Scholars@Duke
James Robert Burke

James Robert Burke

Professor of Neurology
Neurology, Behavioral Neurology
Duke Box 3333, Room 201 B Bryan Research Bldg, Durham, NC 27710
932 Morreene Rd, Box 2900, Durham, NC 27710

Selected Publications

Beta amyloid PET scans for dementia diagnoses: Practice and research implications from CARE-IDEAS.

Journal Article J Am Geriatr Soc · October 2024 Beta amyloid PET scans are a minimally invasive biomarker that may inform Alzheimer's disease (AD) diagnosis. The Caregiver's Reactions and Experience (CARE) study, an IDEAS supplement, aimed to understand experiences of PET scan recipients and their care ... Full text Link to item Cite

Association between results of an amyloid PET scan and healthcare utilization in individuals with cognitive impairment.

Journal Article J Am Geriatr Soc · March 2024 BACKGROUND: The Imaging Dementia Evidence for Amyloid Scanning (IDEAS) study reports that amyloid PET scans help providers diagnose and manage Alzheimer's disease and related dementias (ADRD). Using CARE-IDEAS, an IDEAS supplemental study, we examined the ... Full text Link to item Cite

Elevated Amyloid-β PET Scan and Cognitive and Functional Decline in Mild Cognitive Impairment and Dementia of Uncertain Etiology.

Journal Article J Alzheimers Dis · 2024 BACKGROUND: Elevated amyloid-β (Aβ) on positron emission tomography (PET) scan is used to aid diagnosis of Alzheimer's disease (AD), but many prior studies have focused on patients with a typical AD phenotype such as amnestic mild cognitive impairment (MCI ... Full text Link to item Cite

Prevalence and incidence of depressive symptoms and diagnosis of depression as associated with elevated amyloid among Medicare beneficiaries with cognitive impairment.

Journal Article J Affect Disord · August 1, 2023 BACKGROUND: Depression and cognitive impairment commonly co-occur, and it has been hypothesized that the two share pathological processes. Our objective for this study was to determine the relationship between elevated β-amyloid level and the prevalence an ... Full text Link to item Cite

The Preventing Alzheimer's with Cognitive Training (PACT) randomized clinical trial.

Journal Article Contemp Clin Trials · December 2022 BACKGROUND: To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially av ... Full text Link to item Cite

Manifestations of Alzheimer's disease genetic risk in the blood are evident in a multiomic analysis in healthy adults aged 18 to 90.

Journal Article Sci Rep · April 12, 2022 Genetics play an important role in late-onset Alzheimer's Disease (AD) etiology and dozens of genetic variants have been implicated in AD risk through large-scale GWAS meta-analyses. However, the precise mechanistic effects of most of these variants have y ... Full text Link to item Cite

Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation.

Journal Article Acta Neuropathol Commun · March 3, 2022 Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 and TSC2 genes and autosomal dominantly inherited. These mutations cause hyperactivation of the mammalian Target of Rapamycin (mTOR) pathway, leading to the d ... Full text Link to item Cite

Convolutional neural network to identify symptomatic Alzheimer's disease using multimodal retinal imaging.

Journal Article Br J Ophthalmol · March 2022 BACKGROUND/AIMS: To develop a convolutional neural network (CNN) to detect symptomatic Alzheimer's disease (AD) using a combination of multimodal retinal images and patient data. METHODS: Colour maps of ganglion cell-inner plexiform layer (GC-IPL) thicknes ... Full text Open Access Link to item Cite

Amyloid-β PET Scan Results Disclosure and Care-Partner Emotional Well-Being Over Time.

Journal Article J Alzheimers Dis · 2022 BACKGROUND: Diagnostic tests, such as amyloid-β positron emission tomography (PET) scans, can increase appropriate therapeutic management for the underlying causes of cognitive decline. To evaluate the full utility of this diagnostic tool, information is n ... Full text Link to item Cite

Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial.

Journal Article Lancet Neurol · July 2021 BACKGROUND: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify par ... Full text Link to item Cite

Assessing the Retinal Microvasculature in Individuals With Early and Late-Onset Alzheimer's Disease.

Journal Article Ophthalmic Surg Lasers Imaging Retina · June 2021 BACKGROUND AND OBJECTIVE: To evaluate retinal microvascular changes in early and late-onset Alzheimer's disease (AD). PATIENTS AND METHODS: Eighty-six eyes of 50 late-onset AD participants, 27 eyes of 15 early onset AD participants, and 111 eyes of 57 cogn ... Full text Link to item Cite

Subjective Cognitive Decline

Chapter · January 1, 2021 Full text Cite

Association of OCT Angiography Parameters With Age in Cognitively Healthy Older Adults.

Journal Article Ophthalmic Surg Lasers Imaging Retina · December 1, 2020 BACKGROUND AND OBJECTIVE: To evaluate the association of changes in retinal anatomy and microvasculature with age and sex in cognitively healthy older adults. PATIENTS AND METHODS: Cross-sectional study of cognitively healthy subjects aged 50 years and old ... Full text Link to item Cite

Measurement Properties of the CAPACITY Instrument to Assess Perceived Communication With the Health Care Team Among Care Partners of Patients With Cognitive Impairment.

Journal Article Med Care · September 2020 BACKGROUND: The CAregiver Perceptions About CommunIcaTion with Clinical Team members (CAPACITY) instrument measures how care partners perceive themselves to be supported by the patient's health care team and their experiences communicating with the team. O ... Full text Link to item Cite

Racially diverse participant registries to facilitate the recruitment of African Americans into presymptomatic Alzheimer's disease studies.

Journal Article Alzheimers Dement · August 2020 INTRODUCTION: The Alzheimer's Disease Prevention Registry (ADPR) of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center at Duke University has been successful in achieving a racially diverse and "research ready" cohort of cognitively healthy ... Full text Link to item Cite

Longer Term Effects of Diet and Exercise on Neurocognition: 1-Year Follow-up of the ENLIGHTEN Trial.

Journal Article J Am Geriatr Soc · March 2020 OBJECTIVES: To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention. DESIGN: A 2 (Exerci ... Full text Link to item Cite

Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.

Journal Article Nat Commun · February 3, 2020 Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a part ... Full text Link to item Cite

How Accurately Do Patients and Their Care Partners Report Results of Amyloid-β PET Scans for Alzheimer's Disease Assessment?

Journal Article J Alzheimers Dis · 2020 BACKGROUND: Amyloid-β PET scans will likely become an integral part of the diagnostic evaluation for Alzheimer's disease if Medicare approves reimbursement for the scans. However, little is known about patients' and their care partners' interpretation of s ... Full text Link to item Cite

Metabolic and Neurocognitive Changes Following Lifestyle Modification: Examination of Biomarkers from the ENLIGHTEN Randomized Clinical Trial.

Journal Article J Alzheimers Dis · 2020 BACKGROUND: Previous studies have demonstrated that aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet can improve neurocognition. However, the mechanisms by which lifestyle improves neurocognition have not been widely studie ... Full text Link to item Cite

Correlation of OCTA and Volumetric MRI in Mild Cognitive Impairment and Alzheimer's Disease.

Journal Article Ophthalmic Surg Lasers Imaging Retina · November 1, 2019 BACKGROUD AND OBJECTIVE: To evaluate the relationship between retinal microvascular parameters on optical coherence tomography angiography (OCTA) and neurodegenerative changes assessed by measurement of brain volume on volumetric magnetic resonance imaging ... Full text Link to item Cite

Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Journal Article Nat Genet · September 2019 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype.

Journal Article JAMA Neurol · September 1, 2019 IMPORTANCE: Previous genome-wide association studies of common variants identified associations for Alzheimer disease (AD) loci evident only among individuals with particular APOE alleles. OBJECTIVE: To identify APOE genotype-dependent associations with in ... Full text Link to item Cite

CpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease.

Journal Article Aging Cell · August 2019 CpG-related single nucleotide polymorphisms (CGS) have the potential to perturb DNA methylation; however, their effects on Alzheimer disease (AD) risk have not been evaluated systematically. We conducted a genome-wide association study using a sliding-wind ... Full text Link to item Cite

Determination of Real Time in Vivo Drug Receptor Occupancy for a Covalent Binding Drug as a Clinical Pharmacodynamic Biomarker by Immunocapture-LC-MS/MS.

Journal Article Anal Chem · July 2, 2019 We report a novel immunocapture (IC)-LC-MS/MS methodology to directly measure real time in vivo receptor occupancy (RO) for a covalent binding drug in blood lysate. A small molecule quencher was added immediately after sample collection to convert the free ... Full text Link to item Cite

Deep learning algorithm for diagnosis of Alzheimer's disease using multimodal retinal imaging

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

Retinal Microvascular and Neurodegenerative Changes in Alzheimer's Disease and Mild Cognitive Impairment Compared with Control Participants.

Journal Article Ophthalmol Retina · June 2019 PURPOSE: Evaluate and compare the retinal microvasculature in the superficial capillary plexus (SCP) in Alzheimer's disease (AD), mild cognitive impairment (MCI), and cognitively intact controls using OCT angiography. OCT parameters were also compared. DES ... Full text Link to item Cite

Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Journal Article Nat Genet · March 2019 Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confi ... Full text Link to item Cite

A statistical framework for cross-tissue transcriptome-wide association analysis.

Journal Article Nat Genet · March 2019 Transcriptome-wide association analysis is a powerful approach to studying the genetic architecture of complex traits. A key component of this approach is to build a model to impute gene expression levels from genotypes by using samples with matched genoty ... Full text Link to item Cite

Lifestyle and neurocognition in older adults with cognitive impairments: A randomized trial.

Journal Article Neurology · January 15, 2019 OBJECTIVE: To determine the independent and additive effects of aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet on executive functioning in adults with cognitive impairments with no dementia (CIND) and risk factors for car ... Full text Link to item Cite

Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level-dependent functional magnetic resonance imaging study in elderly adults.

Journal Article Alzheimers Dement (N Y) · 2019 INTRODUCTION: Mitochondrial dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). Accordingly, drugs that positively influence mitochondrial function are being evaluated in delay-of-onset clinical trials with at-risk individuals. Su ... Full text Link to item Cite

Association Between Insulin Resistance, Plasma Leptin, and Neurocognition in Vascular Cognitive Impairment.

Journal Article J Alzheimers Dis · 2019 BACKGROUND: Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated. OBJECTIVE: To examine metabolic mechanisms underlyi ... Full text Link to item Cite

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Journal Article Acta Neuropathol · December 2018 Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of ... Full text Link to item Cite

Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau.

Journal Article JAMA Neurol · August 1, 2018 IMPORTANCE: The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neur ... Full text Link to item Cite

Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial.

Journal Article JAMA Neurol · July 1, 2018 IMPORTANCE: Nerve growth factor (NGF) is an endogenous neurotrophic factor that prevents the death and augments the functional state of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease ... Full text Link to item Cite

Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer's disease.

Journal Article PLoS One · 2018 Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninv ... Full text Link to item Cite

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Journal Article Alzheimer S and Dementia Diagnosis Assessment and Disease Monitoring · January 1, 2018 Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered ... Full text Cite

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

Journal Article Nat Genet · September 2017 We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) ... Full text Link to item Cite

Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

Journal Article Alzheimers Dement · July 2017 INTRODUCTION: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. METHODS: We conducted a transethnic genome-wide association study (G ... Full text Link to item Cite

A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging.

Journal Article Alzheimers Dement (Amst) · 2017 INTRODUCTION: Changes in cerebrospinal fluid (CSF) tau and amyloid β (Aβ)42 accompany development of Alzheimer's brain pathology. Robust tau and Aβ42 immunoassays were developed to establish a tau/Aβ42 cutoff distinguishing mild-to-moderate Alzheimer's dis ... Full text Link to item Cite

Lifestyle and Neurocognition in Older Adults With Cardiovascular Risk Factors and Cognitive Impairment.

Journal Article Psychosom Med · 2017 OBJECTIVE: The aim of the study was to determine the relationship of lifestyle factors and neurocognitive functioning in older adults with vascular risk factors and cognitive impairment, no dementia (CIND). METHODS: One hundred sixty adults (M [SD] = 65.4 ... Full text Link to item Cite

Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A Reversible Inhibitor of Bruton's Tyrosine Kinase (BTK) Conformationally Constrained by Two Locked Atropisomers.

Journal Article J Med Chem · October 13, 2016 Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in ma ... Full text Link to item Cite

Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177).

Journal Article J Med Chem · September 8, 2016 Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) lea ... Full text Link to item Cite

Retinal Biomarkers of Alzheimer's Disease

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

Assessment of the genetic variance of late-onset Alzheimer's disease.

Journal Article Neurobiol Aging · May 2016 Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Tr ... Full text Link to item Cite

Epigenetic assimilation in the aging human brain.

Journal Article Genome Biol · April 28, 2016 BACKGROUND: Epigenetic drift progressively increases variation in DNA modification profiles of aging cells, but the finale of such divergence remains elusive. In this study, we explored the dynamics of DNA modification and transcription in the later stages ... Full text Link to item Cite

Prefrontal contributions to relational encoding in amnestic mild cognitive impairment.

Journal Article Neuroimage Clin · 2016 Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI). Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies us ... Full text Link to item Cite

Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci.

Journal Article PLoS One · 2016 Late onset Alzheimer's disease (LOAD) is a genetically complex and clinically heterogeneous disease. Recent large-scale genome wide association studies (GWAS) have identified more than twenty loci that modify risk for AD. Despite the identification of thes ... Full text Link to item Cite

A Genetics-based Biomarker Risk Algorithm for Predicting Risk of Alzheimer's Disease.

Journal Article Alzheimers Dement (N Y) · January 1, 2016 BACKGROUND: A straightforward, reproducible blood-based test that predicts age dependent risk of Alzheimer's disease (AD) could be used as an enrichment tool for clinical development of therapies. This study evaluated the prognostic performance of a geneti ... Full text Link to item Cite

A novel Alzheimer disease locus located near the gene encoding tau protein.

Journal Article Mol Psychiatry · January 2016 APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10  ... Full text Link to item Cite

Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses.

Journal Article Alzheimers Dement · December 2015 Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that ... Full text Link to item Cite

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals.

Journal Article JAMA Neurol · November 2015 IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROH ... Full text Link to item Cite

A Plan for Academic Biobank Solvency-Leveraging Resources and Applying Business Processes to Improve Sustainability.

Journal Article Clin Transl Sci · October 2015 Researcher-initiated biobanks based at academic institutions contribute valuable biomarker and translational research advances to medicine. With many legacy banks once supported by federal funding, reductions in fiscal support threaten the future of existi ... Full text Link to item Cite

Stability of Diagnoses of Cognitive Impairment, Not Dementia in a Veterans Affairs Primary Care Population.

Journal Article J Am Geriatr Soc · June 2015 OBJECTIVES: To describe the stability of cognitive impairment, not dementia (CIND) in a longitudinal cohort of primary care veterans. To examine the association between baseline brief cognitive screening tests, demographic and clinical characteristics, and ... Full text Link to item Cite

Retinal imaging biomarkers for early diagnosis of Alzheimer's disease

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2015 Link to item Cite

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

Journal Article PLoS Med · June 2015 BACKGROUND: Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We ... Full text Link to item Cite

Rarity of the Alzheimer disease-protective APP A673T variant in the United States.

Journal Article JAMA Neurol · February 2015 IMPORTANCE: Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer di ... Full text Link to item Cite

Factors associated with cognitive evaluations in the United States.

Journal Article Neurology · January 6, 2015 OBJECTIVE: We aimed to explore factors associated with clinical evaluations for cognitive impairment among older residents of the United States. METHODS: Two hundred ninety-seven of 845 subjects in the Aging, Demographics, and Memory Study (ADAMS), a natio ... Full text Link to item Cite

Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.

Journal Article JAMA Neurol · November 2014 IMPORTANCE: Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. OBJECTIVE ... Full text Link to item Cite

Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study.

Journal Article Neurobiol Aging · November 2014 Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer's disease (AD), it remains unclear which class provides the most benefit. The Cache County Study of Memory Health and Aging is a prospective longitudinal co ... Full text Link to item Cite

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

Journal Article Am J Geriatr Psychiatry · November 2014 BACKGROUND: Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be mor ... Full text Link to item Cite

The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes.

Journal Article Alzheimers Dement · September 2014 BACKGROUND: We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) t ... Full text Link to item Cite

Impact of ¹⁸F-florbetapir PET imaging of β-amyloid neuritic plaque density on clinical decision-making.

Journal Article Neurocase · August 2014 ¹⁸F-florbetapir positron emission tomography (PET) imaging of the brain is now approved by the Food and Drug Administration (FDA) approved for estimation of β -amyloid neuritic plaque density when evaluating patients with cognitive impairment. However, its ... Full text Link to item Cite

Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine diseases.

Journal Article Neurotherapeutics · July 2013 Protein misfolding and aggregation in the brain have been recognized to be crucial in the pathogenesis of various neurodegenerative diseases, including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases, which are collectively called the "pro ... Full text Link to item Cite

Phenotypic regional functional imaging patterns during memory encoding in mild cognitive impairment and Alzheimer's disease.

Journal Article Alzheimers Dement · May 2013 BACKGROUND: Reliable blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggreg ... Full text Open Access Link to item Cite

Neuropsychological predictors of dementia in late-life major depressive disorder.

Journal Article Am J Geriatr Psychiatry · March 2013 OBJECTIVE: Major depressive disorder is a likely risk factor for dementia, but some cases of major depressive disorder in older adults may actually represent a prodrome of this condition. The purpose of this study was to use neuropsychological test scores ... Full text Link to item Cite

Using genetics to enable studies on the prevention of Alzheimer's disease.

Journal Article Clin Pharmacol Ther · February 2013 Curing Alzheimer's disease (AD) remains an elusive goal; indeed, it may even prove to be impossible, given the nature of the disease. Although modulating disease progression is an attractive target and will alleviate the burden of the most severe stages, t ... Full text Link to item Cite

Can lifestyle modification improve neurocognition? Rationale and design of the ENLIGHTEN clinical trial.

Journal Article Contemp Clin Trials · January 2013 BACKGROUND: Risk factors for cardiovascular disease (CVD) not only increase the risk for clinical CVD events, but also are associated with a cascade of neurophysiologic and neuroanatomic changes that increase the risk of cognitive impairment and dementia. ... Full text Link to item Cite

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.

Journal Article Nat Genet · December 2012 Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were assoc ... Full text Link to item Cite

Event-related functional magnetic resonance imaging changes during relational retrieval in normal aging and amnestic mild cognitive impairment.

Journal Article J Int Neuropsychol Soc · September 2012 The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely refl ... Full text Link to item Cite

Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases.

Journal Article Hum Mol Genet · August 1, 2012 Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype ... Full text Link to item Cite

The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression.

Journal Article Neurobiol Aging · July 2012 SORL1 has been identified as a major contributor to late onset Alzheimer's disease (LOAD). We test whether genetic variability in the 5' of SORL1 gene modulates the risk to develop LOAD via regulation of SORL1-messenger ribonucleic acid (mRNA) expression a ... Full text Link to item Cite

Screening for cognitive impairment: comparing the performance of four instruments in primary care.

Journal Article J Am Geriatr Soc · June 2012 OBJECTIVES: To determine whether brief cognitive screening tests perform as well as a longer screening test in diagnosis of cognitive impairment, no dementia (CIND) or dementia. DESIGN: A cross-sectional comparison of cognitive screening tests to an indepe ... Full text Link to item Cite

Sound induced vertigo: superior canal dehiscence resulting from blast exposure.

Journal Article Arch Phys Med Rehabil · April 2012 Barotrauma is common in modern warfare. We present the first description of sound induced vertigo caused by superior canal dehiscence (SCD) precipitated by blast exposure. Patients who complain of balance or visual changes after military or terrorist blast ... Full text Link to item Cite

Neuropsychological Predictors of Dementia in Late-Life Major Depressive Disorder.

Journal Article Am J Geriatr Psychiatry · March 11, 2012 OBJECTIVE:: Major depressive disorder is a likely risk factor for dementia, but some cases of major depressive disorder in older adults may actually represent a prodrome of this condition. The purpose of this study was to use neuropsychological test scores ... Full text Link to item Cite

Incidence of dementia and cognitive impairment, not dementia in the United States.

Journal Article Ann Neurol · September 2011 OBJECTIVE: Estimates of incident dementia, and cognitive impairment, not dementia (CIND) (or the related mild cognitive impairment) are important for public health and clinical care policy. In this paper, we report US national incidence rates for dementia ... Full text Link to item Cite

Risk factors and preventive interventions for Alzheimer disease: state of the science.

Journal Article Arch Neurol · September 2011 BACKGROUND: Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any m ... Full text Link to item Cite

An international perspective on advanced neuroimaging: cometh the hour or ivory tower?

Journal Article Int Psychogeriatr · September 2011 Over the past five to ten years, neuroimaging capability for neurodegenerative diseases has made remarkable progress. However, debate remains as to the true clinical utility of these advanced and costly investigations. Not only is the place of these tests ... Full text Link to item Cite

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

Journal Article Nat Genet · May 2011 The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis ... Full text Link to item Cite

Metabolomic changes in autopsy-confirmed Alzheimer's disease.

Journal Article Alzheimers Dement · May 2011 BACKGROUND: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insight ... Full text Link to item Cite

Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors.

Journal Article Arch Neurol · March 2011 OBJECTIVE: To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD) ... Full text Link to item Cite

The effect of SNCA 3' region on the levels of SNCA-112 splicing variant.

Journal Article Neurogenetics · February 2011 Genetic variability at the 3' region of SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson's disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However, the ... Full text Link to item Cite

Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: synthesis, SAR, PK/PD and activity in a preclinical model of rheumatoid arthritis.

Journal Article Bioorg Med Chem Lett · January 1, 2011 The synthesis, structure-activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be orally efficacious in a murine model of rheumatoid arthritis. ... Full text Link to item Cite

Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.

Journal Article PLoS One · 2011 BACKGROUND: The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and ... Full text Link to item Cite

The Aggregation Inhibitor Peptide QBP1 as a Therapeutic Molecule for the Polyglutamine Neurodegenerative Diseases.

Journal Article J Amino Acids · 2011 Misfolding and abnormal aggregation of proteins in the brain are implicated in the pathogenesis of various neurodegenerative diseases including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases. In the polyQ diseases, an abnormally expanded ... Full text Link to item Cite

Validation of consensus panel diagnosis in dementia.

Journal Article Arch Neurol · December 2010 BACKGROUND: The clinical diagnosis of dementing diseases largely depends on the subjective interpretation of patient symptoms. Consensus panels are frequently used in research to determine diagnoses when definitive pathologic findings are unavailable. Neve ... Full text Link to item Cite

Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life.

Journal Article Ann Intern Med · August 3, 2010 BACKGROUND: Many biological, behavioral, social, and environmental factors may contribute to the delay or prevention of cognitive decline. PURPOSE: To summarize evidence about putative risk and protective factors for cognitive decline in older adults and t ... Full text Link to item Cite

Temporal lobe functional activity and connectivity in young adult APOE varepsilon4 carriers.

Journal Article Alzheimers Dement · July 2010 BACKGROUND: We sought to determine if the APOE epsilon4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTLs) during successful memory encoding in young adults. METHODS: Twenty-four healthy young adults, i.e. ... Full text Link to item Cite

Preventing Alzheimer's disease and cognitive decline.

Journal Article Evid Rep Technol Assess (Full Rep) · April 2010 OBJECTIVES: To assess whether previous research on purported risk or protective factors for Alzheimer's disease (AD) and cognitive decline is of sufficient strength to warrant specific recommendations for behavioral, lifestyle, or pharmaceutical interventi ... Link to item Cite

Genome-wide scan of copy number variation in late-onset Alzheimer's disease.

Journal Article J Alzheimers Dis · 2010 Featured Publication Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence d ... Full text Open Access Link to item Cite

Cognitive performance and informant reports in the diagnosis of cognitive impairment and dementia in African Americans and whites.

Journal Article Alzheimers Dement · November 2009 BACKGROUND: The diagnosis of cognitive impairment and dementia must reflect an increasingly diverse and aging United States population. This study compared direct testing and informant reports of cognition with clinical diagnoses of cognitive impairment an ... Full text Link to item Cite

Genetic regulation of alpha-synuclein mRNA expression in various human brain tissues.

Journal Article PLoS One · October 16, 2009 Genetic variability across the SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson's disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However whether genet ... Full text Link to item Cite

Cognitive functioning in Alzheimer's and vascular dementia: a meta-analysis.

Journal Article Neuropsychology · July 2009 Differentiating between Alzheimer's disease (AD) and vascular dementia (VaD) remains difficult but important if existing pharmacological treatments are to provide symptomatic relief in the case of AD or to alter disease progression in the case of VaD. Cogn ... Full text Link to item Cite

Synthesis, initial SAR and biological evaluation of 1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine derived inhibitors of IkappaB kinase.

Journal Article Bioorg Med Chem Lett · May 15, 2009 A new series of tricyclic-based inhibitors of IKK have been derived from an earlier lead compound. The synthesis and structure-activity relationships (SAR) are described. Compound 4k inhibited TNF production in rats stimulated with LPS. ... Full text Link to item Cite

Twin pairs discordant for neuropathologically confirmed Lewy body dementia.

Journal Article J Neurol Neurosurg Psychiatry · May 2009 Featured Publication AIM: Little is known about the concordance rate in twins for dementia with Lewy bodies (DLB). The rate of agreement between clinical and pathological diagnoses for DLB is typically low, necessitating confirmation of the diagnosis neuropathologically. METHO ... Full text Link to item Cite

Cerebrovascular smooth muscle actin is increased in nondemented subjects with frequent senile plaques at autopsy: implications for the pathogenesis of Alzheimer disease.

Journal Article J Neuropathol Exp Neurol · April 2009 We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared with brains of nondemented, neuropathologically normal subjects. To assess the pathogenetic significance and di ... Full text Link to item Cite

Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries.

Journal Article Chem Biol · September 22, 2008 Human tissue transglutaminase (TGM2) is a calcium-dependent crosslinking enzyme involved in the posttranslational modification of intra- and extracellular proteins and implicated in several neurodegenerative diseases. To find specific inhibitors to TGM2, t ... Full text Link to item Cite

Midlife activity predicts risk of dementia in older male twin pairs.

Journal Article Alzheimers Dement · September 2008 BACKGROUND: This was a prospective study of dementia to elucidate mechanisms of disease risk factors amenable to modification and specifically to determine whether midlife cognitive and physical leisure activities are associated with delayed onset or reduc ... Full text Link to item Cite

A novel human disease with abnormal prion protein sensitive to protease.

Journal Article Ann Neurol · June 2008 Featured Publication OBJECTIVE: To report a novel prion disease characterized by distinct histopathological and immunostaining features, and associated with an abnormal isoform of the prion protein (PrP) that, contrary to the common prion diseases, is predominantly sensitive t ... Full text Link to item Cite

Neuroanatomical correlates of malingered memory impairment: event-related fMRI of deception on a recognition memory task.

Journal Article Brain Inj · June 2008 PRIMARY OBJECTIVE: Event-related, functional magnetic resonance imaging (fMRI) data were acquired in healthy participants during purposefully malingered and normal recognition memory performances to evaluate the neural substrates of feigned memory impairme ... Full text Link to item Cite

Prevalence of cognitive impairment without dementia in the United States.

Journal Article Ann Intern Med · March 18, 2008 Featured Publication BACKGROUND: Cognitive impairment without dementia is associated with increased risk for disability, increased health care costs, and progression to dementia. There are no population-based prevalence estimates of this condition in the United States. OBJECTI ... Full text Link to item Cite

Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study.

Journal Article Int J Geriatr Psychiatry · February 2008 BACKGROUND: Neuropsychiatric symptoms are nearly universal in dementia, yet little is known about their longitudinal course in the community. OBJECTIVE: To estimate point and 5-year period prevalence of neuropsychiatric symptoms in an incident sample of 40 ... Full text Link to item Cite

A novel human disease with abnormal prion protein sensitive to protease

Conference JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY · 2008 Cite

Postmortem delay has minimal effect on brain RNA integrity.

Journal Article J Neuropathol Exp Neurol · December 2007 The Bryan Alzheimer Disease Research Center obtains postmortem human brain tissue from patients with Alzheimer disease (AD) and cognitively normal control subjects for molecular and genetic research programs. A growing body of research suggests that variat ... Full text Link to item Cite

Optimization of a polyglutamine aggregation inhibitor peptide (QBP1) using a thioflavin T fluorescence assay.

Journal Article Assay Drug Dev Technol · October 2007 Polyglutamine protein aggregates are a hallmark of several neurodegenerative diseases, including Huntington's disease, and increasing evidence suggests that reducing or inhibiting aggregation produces a therapeutic benefit in animal models of disease. Part ... Full text Link to item Cite

Longitudinal magnetic resonance imaging vascular changes, apolipoprotein E genotype, and development of dementia in the neurocognitive outcomes of depression in the elderly study.

Journal Article Am J Geriatr Psychiatry · October 2007 OBJECTIVE: Several studies suggest that depression is a risk factor for development of dementia in the elderly. In a study of older depressed individuals, the authors examined both neuroimaging and genetic factors in development of dementia. The authors hy ... Full text Link to item Cite

Autopsy-confirmed Alzheimer's disease versus clinically diagnosed Alzheimer's disease in the Cache County Study on Memory and Aging: a comparison of quantitative MRI and neuropsychological findings.

Journal Article J Clin Exp Neuropsychol · July 2007 Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically ... Full text Link to item Cite

Job demands and dementia risk among male twin pairs.

Journal Article Alzheimers Dement · July 2007 BACKGROUND: Job characteristics may influence dementia risk, but some types of job complexity remain to be examined. Twin studies provide a useful methodology to examine job differences between pairs who share many environmental and genetic influences. MET ... Full text Link to item Cite

Arteriolar ApoE expression is increased Alzheimer disease cortex

Conference Journal of Neuropathology and Experimental Neurology · May 2007 Full text Cite

Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease.

Journal Article Genome Biol · 2007 BACKGROUND: Alternative gene transcript splicing permits a single gene to produce multiple proteins with varied functions. Bioinformatic investigations have identified numerous splice variants, but whether these transcripts are translated to functional pro ... Full text Link to item Cite

Prevalence of dementia in the United States: the aging, demographics, and memory study.

Journal Article Neuroepidemiology · 2007 Featured Publication AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the ... Full text Link to item Cite

Duke Twins Study of Memory in Aging in the NAS-NRC Twin Registry.

Journal Article Twin Res Hum Genet · December 2006 The Duke Twins Study of Memory in Aging is an ongoing, longitudinal study of cognitive change and dementia in the population-based National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry of World War II Male Veterans. The primary goa ... Full text Link to item Cite

A human prion disease with protease-sensitive prion

Conference BRAIN PATHOLOGY · September 1, 2006 Link to item Cite

A population-based study of the association between coronary artery bypass graft surgery (CABG) and cognitive decline: the Cache County study.

Journal Article Int J Geriatr Psychiatry · June 2006 BACKGROUND: The relationship between coronary artery bypass graft (CABG) surgery and cognitive decline remains uncertain, in particular with regard to whether there is delayed cognitive decline associated with this procedure. METHODS: This was a population ... Full text Link to item Cite

Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria.

Journal Article Biochem Biophys Res Commun · March 10, 2006 Huntington's disease results from expansion of the polyglutamine (PolyQ) domain in the huntingtin protein. Although the cellular mechanism by which pathologic-length PolyQ protein causes neurodegeneration is unclear, mitochondria appear central in pathogen ... Full text Link to item Cite

Phage display screening for peptides that inhibit polyglutamine aggregation.

Journal Article Methods Enzymol · 2006 Proteins with expanded polyglutamine domains cause nine dominantly inherited, neurodegenerative diseases, including Huntington's disease. There are no therapies that inhibit disease onset or progression. To identify a novel therapeutic, we screened phage d ... Full text Link to item Cite

Comparison of clinical and neuropathologic diagnoses of Alzheimer's disease in 3 epidemiologic samples.

Journal Article Alzheimers Dement · January 2006 BACKGROUND: Studies of dementia in populations avoid many of the selection biases in clinical samples but require special evaluation and diagnostic methods to obtain high participation rates. To address this issue, we developed a unique in-home dementia as ... Full text Link to item Cite

Emotional enhancement of perceptual priming is preserved in aging and early-stage Alzheimer's disease.

Journal Article Neuropsychologia · 2005 Perceptual priming for emotionally-negative and neutral scenes was tested in early-stage Alzheimer's disease (AD) patients and healthy younger, middle-aged and older adults. In the study phase, participants rated the scenes for their arousal properties. In ... Full text Link to item Cite

The Aging, Demographics, and Memory Study: study design and methods.

Journal Article Neuroepidemiology · 2005 Featured Publication OBJECTIVE: We describe the design and methods of the Aging, Demographics, and Memory Study (ADAMS), a new national study that will provide data on the antecedents, prevalence, outcomes, and costs of dementia and "cognitive impairment, not demented" (CIND) ... Full text Link to item Cite

A population study of Alzheimer's disease: findings from the Cache County Study on Memory, Health, and Aging.

Journal Article Care Manag J · 2005 There are several population-based studies of aging, memory, and dementia being conducted worldwide. Of these, the Cache County Study on Memory, Health and Aging is noteworthy for its large number of "oldest-old" members. This study, which has been followi ... Full text Link to item Cite

Methodology and preliminary results from the neurocognitive outcomes of depression in the elderly study.

Journal Article J Geriatr Psychiatry Neurol · December 2004 A methodology is presented for following a cohort of older depressed patients to examine neurocognitive outcomes of depression. A total of 265 depressed individuals and 138 healthy, nondepressed controls age 60 and older who completed at least 1 year of fo ... Full text Link to item Cite

Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.

Journal Article J Neurosci · August 11, 2004 Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of ... Full text Link to item Cite

Disruption of the toxic conformation of the expanded polyglutamine stretch leads to suppression of aggregate formation and cytotoxicity.

Journal Article Biochem Biophys Res Commun · May 14, 2004 The polyglutamine (polyQ) diseases are a class of inherited neurodegenerative diseases including Huntington's disease, caused by the expansion of a polyQ stretch within each disease protein. This expansion is thought to cause a conformational change in the ... Full text Link to item Cite

Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats.

Journal Article J Neurochem · March 2004 The expansion of a polyglutamine (polyQ) domain in neuronal proteins is the molecular genetic cause of at least eight neurodegenerative diseases. Proteins with a polyQ domain that is greater than 40 Q (Q40) residues form insoluble intranuclear and cytoplas ... Full text Link to item Cite

APOE genotype-specific differences in human and mouse macrophage nitric oxide production.

Journal Article J Neuroimmunol · February 2004 Individuals expressing an APOE4 genotype demonstrate increased Alzheimer's disease (AD) neuropathology and a decreased onset age. The APOE4 gene may act by modulating the CNS immune response. Using human monocyte-derived macrophages (MDM), we show a signif ... Full text Link to item Cite

Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila.

Journal Article Hum Mol Genet · June 1, 2003 Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought ... Full text Link to item Cite

Apolipoprotein E genotype and major depression in a community of older adults. The Cache County Study.

Journal Article Psychol Med · April 2003 BACKGROUND: The role of allelic variation in APOE, the genetic locus for apolipoprotein E, in geriatric depression is poorly understood. There are conflicting reports as to an association between the epsilon4 allele and depression in late life. METHOD: Usi ... Full text Link to item Cite

In vitro effects of polyglutamine tracts on Ca2+-dependent depolarization of rat and human mitochondria: relevance to Huntington's disease.

Journal Article Arch Biochem Biophys · February 1, 2003 The mechanisms by which neurons die in CAG triplet repeat (polyglutamine) disorders, such as Huntington's disease, are uncertain; however, mitochondrial dysfunction and disordered calcium homeostasis have been implicated. We previously demonstrated abnorma ... Full text Link to item Cite

Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines.

Journal Article Nat Neurosci · August 2002 Huntington's disease (HD) is caused by an expansion of exonic CAG triplet repeats in the gene encoding huntingtin protein (Htt), but the mechanisms by which this mutant protein causes neurodegeneration remain unknown. Here we show that lymphoblast mitochon ... Full text Link to item Cite

Expanded polyglutamine stretches form an 'aggresome'.

Journal Article Neurosci Lett · May 3, 2002 To understand the pathogenetic mechanisms underlying polyglutamine (polyQ) diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA). We demon ... Full text Link to item Cite

An adaptation of the modified mini-mental state examination: analysis of demographic influences and normative data: the cache county study.

Journal Article Neuropsychiatry Neuropsychol Behav Neurol · March 2002 OBJECTIVES: To present a new version of the Modified Mini-Mental State Examination (3MS-R), provide normative information extending to individuals in the 10th decade, and examine the effects of demographic variables on test performance. BACKGROUND: The Mod ... Link to item Cite

Amino acid sequence requirements of peptides that inhibit polyglutamine-protein aggregation and cell death.

Journal Article Biochem Biophys Res Commun · November 2, 2001 Proteins with expanded polyglutamine domains cause eight inherited neurodegenerative diseases including Huntington's disease. In a previous paper, we identified peptides that inhibit polyglutamine protein aggregation and cell death and now describe the ami ... Full text Link to item Cite

Documented head injury in early adulthood and risk of stroke in late life.

Journal Article JOURNAL OF THE AMERICAN GERIATRICS SOCIETY · April 1, 2001 Link to item Cite

Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias.

Journal Article Neurology · October 24, 2000 BACKGROUND: The association between antecedent head injury and AD is inconsistent. OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction ... Full text Link to item Cite

Inhibition of polyglutamine protein aggregation and cell death by novel peptides identified by phage display screening.

Journal Article J Biol Chem · April 7, 2000 Proteins with expanded polyglutamine domains cause eight inherited neurodegenerative diseases, including Huntington's, but the molecular mechanism(s) responsible for neuronal degeneration are not yet established. Expanded polyglutamine domain proteins poss ... Full text Link to item Cite

Update on Alzheimer's disease. Promising advances in detection and treatment.

Journal Article Postgrad Med · October 15, 1999 In the past decade, significant progress has been made in the understanding and treatment of Alzheimer's disease. Modest success has been achieved using new drugs in treatment of mild symptoms of the disease. Vitamin E, estrogen, and NSAIDs may slow the pr ... Full text Link to item Cite

Managing common behavioral problems in dementia. How to improve quality of life for patients and families.

Journal Article Postgrad Med · October 15, 1999 Dementia is the most common reason for nursing home placement, and related behavioral symptoms are the primary factors precipitating the decision. Disruptive behaviors such as depression, sleep disturbance, agitation, aggression, and psychosis can tax fami ... Full text Link to item Cite

Pathogenesis of inclusion bodies in (CAG)n/Qn-expansion diseases with special reference to the role of tissue transglutaminase and to selective vulnerability.

Journal Article J Neurochem · March 1999 At least eight neurodegenerative diseases, including Huntington disease, are caused by expansions in (CAG)n repeats in the affected gene and by an increase in the size of the corresponding polyglutamine domain in the expressed protein. A hallmark of severa ... Full text Link to item Cite

Expanded polyglutamine domain proteins bind neurofilament and alter the neurofilament network.

Journal Article Exp Neurol · February 1999 Eight inherited neurodegenerative diseases are caused by genes with expanded CAG repeats coding for polyglutamine domains in the disease-producing proteins. The mechanism by which this expanded polyglutamine domain causes neurodegenerative disease is unkno ... Full text Link to item Cite

Generation of neuronal intranuclear inclusions by polyglutamine-GFP: analysis of inclusion clearance and toxicity as a function of polyglutamine length.

Journal Article J Neurosci · January 15, 1999 Recent evidence suggests that, in huntingtin and many other proteins, polyglutamine repeats are a toxic stimulus in neurodegenerative diseases. To investigate the mechanism by which these repeats may be toxic, we transfected primary rat cerebellar granule ... Full text Link to item Cite

Polyglutamine domain proteins with expanded repeats bind neurofilament, altering the neurofilament network.

Journal Article Ann N Y Acad Sci · 1999 Proteins with expanded polyglutamine (polyQ) repeats cause eight inherited neurodegenerative diseases. Nuclear and cytoplasmic polyQ protein is a common feature of these diseases, but its role in cell death remains debatable. Since the neuronal intermediat ... Full text Link to item Cite

A beta-lactam inhibitor of cytosolic phospholipase A2 which acts in a competitive, reversible manner at the lipid/water interface.

Journal Article J Enzyme Inhib · June 1998 Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of phospholipids and is believed to play a key cellular role in the generation of arachidonic acid. When assaying the human recombinant cPLA2 usin ... Full text Link to item Cite

The multisubunit IkappaB kinase complex shows random sequential kinetics and is activated by the C-terminal domain of IkappaB alpha.

Journal Article J Biol Chem · May 15, 1998 The multisubunit IkappaB kinase (IKK) catalyzes the signal-inducible phosphorylation of N-terminal serines of IkappaB. This phosphorylation is the key step in regulating the subsequent ubiquitination and proteolysis of IkappaB, which then releases NF-kappa ... Full text Link to item Cite

Glyceraldehyde 3-phosphate dehydrogenase abnormality in metabolically stressed Huntington disease fibroblasts.

Journal Article Dev Neurosci · 1998 Huntington disease (HD) fibroblasts subjected to stress exhibit an enzyme profile that is different from that exhibited by escapee (unaffected members of families with HD) or control fibroblasts. The specific activity of glyceraldehyde 3-phosphate dehydrog ... Full text Link to item Cite

Inhibition of α-ketoglutarate-and pyruvate dehydrogenase complexes in E. coli by a glutathione S-transferase containing a pathological length poly-Q domain: A possible role of energy deficit in neurological diseases associated with poly-Q expansions?

Journal Article Age (Omaha) · January 1998 At least seven adult-onset neurodegenerative diseases, including Huntington's disease (HD), are caused by genes containing expanded CAG triplets within their coding regions. The expanded CAG repeats give rise to extended stretches of polyglutamines (Qn) in ... Full text Link to item Cite

Transglutaminase-catalyzed inactivation of glyceraldehyde 3-phosphate dehydrogenase and alpha-ketoglutarate dehydrogenase complex by polyglutamine domains of pathological length.

Journal Article Proc Natl Acad Sci U S A · November 11, 1997 Several adult-onset neurodegenerative diseases are caused by genes with expanded CAG triplet repeats within their coding regions and extended polyglutamine (Qn) domains within the expressed proteins. Generally, in clinically affected individuals n >/= 40. ... Full text Link to item Cite

Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells.

Journal Article Biochem Biophys Res Commun · September 18, 1997 Six inherited neurologic diseases, including Huntington's disease, result from the expansion of a CAG domain of the disease genes to produce a domain of more than 40 glutamines in the expressed protein. The mechanism by which expansion of this polyglutamin ... Full text Link to item Cite

Polyglutamine domains are substrates of tissue transglutaminase: does transglutaminase play a role in expanded CAG/poly-Q neurodegenerative diseases?

Journal Article J Neurochem · July 1997 Huntington's disease and six other neurodegenerative diseases are associated with abnormal gene products containing expanded polyglutamine (poly-Q; Qn) domains (n > or = 40). In the present work, we show that glutathione S-transferase (GST) fusion proteins ... Full text Link to item Cite

Toxicity of expanded polyglutamine-domain proteins in Escherichia coli.

Journal Article FEBS Lett · December 9, 1996 Five neurodegenerative diseases are caused by proteins with expanded polyglutamine domains. Toxicity of these proteins has been previously identified only in mammals, and no simple model systems are available. In this paper, we demonstrate in E. coli that ... Full text Link to item Cite

Characterizationof dibutyryl cyclic amp treated u937 cells: role of phosphorylation in cpla2 activation

Journal Article FASEB Journal · December 1, 1996 The mechanism(s) responsible for receptor mediated activation of cytosolic phospholipase A2 (cPLA2) has not been fully elucidated, but there is evidence that both protein phosphorylation and calcium-dependent translocation are involved in the regulation of ... Cite

Fmlp stimulates arachidonic acid release in dibutyryl cyclic amp treated u937 cells

Journal Article FASEB Journal · December 1, 1996 Undifferentiated U937 cells contain high amounts of cytosolic phospholipase A2 (cPLA2) but do not release arachidonic acid (AA) when stimulated with calcium ionophores. Treatment with dibutyryl cyclic AMP (cAMP) causes cell surface receptor expr ... Cite

Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease.

Journal Article Lancet · July 13, 1996 BACKGROUND: We aimed to determine the specificity, sensitivity, and predictive value of apolipoprotein E (APOE) genotyping in 67 consecutive patients with clinical diagnoses of sporadic Alzheimer's disease (AD) who underwent necropsy. METHODS: We studied p ... Full text Link to item Cite

Diagnosis of Alzheimer's disease in epidemiologic studies by staged review of clinical data

Journal Article Neuropsychiatry Neuropsychology and Behavioral Neurology · April 1, 1996 We explored the inter-rater agreement and validity of diagnoses of Alzheimer's disease (AD) and other dementias made in an epidemiological study. A previously described protocol for cognitive screening and clinical assessment was applied to a large registr ... Cite

Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH.

Journal Article Nat Med · March 1996 Featured Publication At least five adult-onset neurodegenerative diseases, including Huntingtin disease (HD), and dentatorubral-pallidoluysian atrophy (DRPLA) are produced by genes containing a variably increased CAG repeat within the coding region. The size range of the repea ... Full text Link to item Cite

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Journal Article Neurology · March 1996 Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable conseq ... Full text Link to item Cite

Priming deficits in patients with dementia of the Alzheimer type.

Journal Article Psychol Med · November 1994 In a study that replicated the procedures used by Salmon et al. (1988), the effect on stem completion performance of two different semantic orientation tasks has been assessed in patients with Alzheimer's disease. Previously reported findings of impairment ... Full text Link to item Cite

The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family.

Journal Article Nat Genet · August 1994 Featured Publication Haw River Syndrome (HRS) is a dominant neurodegenerative disease that has affected five generations of an African-American family in rural North Carolina. The disorder represents a unique spectrum of multiple system degenerations resembling Huntington's di ... Full text Link to item Cite

Interrater agreement for diagnosis of Alzheimer's disease: the MIRAGE study.

Journal Article Neurology · April 1994 There are standardized criteria to assist in the diagnosis of Alzheimer's disease (AD), a disorder that lacks unique clinical, morphologic, or biochemical features. Diagnostic reliability of single groups of investigators using these criteria is moderate t ... Full text Link to item Cite

Genetics of Alzheimer's disease.

Journal Article Int J Neurol · 1991 Alzheimer's disease is the leading cause of dementia in the elderly. Most patients do not have an obvious family history and are classified as sporadic. Genetic factors in early and late-onset Alzheimer's disease are now well documented. This paper reviews ... Link to item Cite

Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group.

Journal Article Ann Neurol · June 1990 Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between ... Full text Link to item Cite

Studies on the function of the non-primer tRNAs associated with the 70 S RNA of avian myeloblastosis virus.

Journal Article Biochim Biophys Acta · February 26, 1982 Significant amounts of three tRNAs are associated with the 70 S RNA of avian myeloblastosis virus (AMV). The temperatures at which they are half dissociated from the 70 S RNA in 50 mM NaCl and their respective quantities relative to 35 S RNA are: tRNAArg, ... Full text Link to item Cite