Scholars@Duke
Richard J O'Brien

Richard J O'Brien

Disque D. Deane University Distinguished Professor of Neurology
Neurology

Selected Publications

Racial Disparities in Low-Value Care in the Last Year of Life for Medicare Beneficiaries With Neurodegenerative Disease.

Journal Article Neurol Clin Pract · April 2024 BACKGROUND AND OBJECTIVES: There are racial disparities in health care services received by patients with neurodegenerative diseases, but little is known about disparities in the last year of life, specifically in high-value and low-value care utilization. ... Full text Link to item Cite

Racial/ethnic disparities in dementia incidence, outcomes, and health-care utilization.

Journal Article Alzheimers Dement · June 2023 INTRODUCTION: Racial/ethnic disparities exist in many aspects of health care, but data on racial/ethnic disparities for neurodegenerative diseases (NDDs), such as dementia and Parkinson's disease (PD), are limited. METHODS: We used North and South Carolina ... Full text Link to item Cite

Identifying vulnerable brain networks associated with Alzheimer's disease risk.

Journal Article Cereb Cortex · April 25, 2023 The selective vulnerability of brain networks in individuals at risk for Alzheimer's disease (AD) may help differentiate pathological from normal aging at asymptomatic stages, allowing the implementation of more effective interventions. We used a sample of ... Full text Link to item Cite

Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions.

Journal Article Front Phys · April 2020 Network approaches provide sensitive biomarkers for neurological conditions, such as Alzheimer's disease (AD). Mouse models can help advance our understanding of underlying pathologies, by dissecting vulnerable circuits. While the mouse brain contains less ... Full text Link to item Cite

Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

Journal Article PLoS Med · January 2020 BACKGROUND: There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical ... Full text Link to item Cite

Evaluating Skilled Prehension in Mice Using an Auto-Trainer.

Journal Article J Vis Exp · September 12, 2019 We describe a method to introduce naïve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that permits the mouse to reach out of its cage and retrieve food pellets. Minimal food restriction is employed to ... Full text Link to item Cite

Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease.

Journal Article Alzheimers Dement · January 2019 INTRODUCTION: Primary age-related tauopathy (PART) is a recently described entity that can cause cognitive impairment in the absence of Alzheimer's disease (AD). Here, we compared neuropathological features, tau haplotypes, apolipoprotein E (APOE) genotype ... Full text Link to item Cite

Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology.

Journal Article J Alzheimers Dis · 2019 BACKGROUND: Cholinesterase inhibitors represent three of the four treatments for Alzheimer's disease (AD), and target the pathological reduction of acetylcholine levels. Here we aimed to study the role of other neurotransmitter pathways in AD pathology. OB ... Full text Link to item Cite

A prognostic model of Alzheimer's disease relying on multiple longitudinal measures and time-to-event data.

Journal Article Alzheimers Dement · May 2018 INTRODUCTION: Characterizing progression in Alzheimer's disease is critically important for early detection and targeted treatment. The objective was to develop a prognostic model, based on multivariate longitudinal markers, for predicting progression-free ... Full text Open Access Link to item Cite

Evidence for brain glucose dysregulation in Alzheimer's disease.

Journal Article Alzheimers Dement · March 2018 INTRODUCTION: It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. METHODS: Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentrati ... Full text Link to item Cite

Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases.

Journal Article JAMA Neurol · July 1, 2017 IMPORTANCE: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype ... Full text Link to item Cite

Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism.

Journal Article Acta Neuropathol · June 2017 Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer's disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the "post-GWAS" era. At least 123 ... Full text Link to item Cite

Long-term cortisol measures predict Alzheimer disease risk.

Journal Article Neurology · January 24, 2017 OBJECTIVE: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. METHOD: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longi ... Full text Link to item Cite

Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway.

Journal Article Mol Psychiatry · January 2017 Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that inflammation is closely associated with AD pathogenesis an ... Full text Link to item Cite

Paradoxical Motor Recovery From a First Stroke After Induction of a Second Stroke: Reopening a Postischemic Sensitive Period.

Journal Article Neurorehabil Neural Repair · September 2016 BACKGROUND AND OBJECTIVE: Prior studies have suggested that after stroke there is a time-limited period of increased responsiveness to training as a result of heightened plasticity-a sensitive period thought to be induced by ischemia itself. Using a mouse ... Full text Link to item Cite

Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation.

Journal Article Mol Psychiatry · July 2016 Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer's disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity ... Full text Link to item Cite

Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change.

Journal Article JAMA Neurol · June 1, 2016 IMPORTANCE: Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively n ... Full text Link to item Cite

Relationship between cerebrospinal fluid biomarkers of Alzheimer's disease and cognition in cognitively normal older adults.

Journal Article Neuropsychologia · November 2015 The pathophysiological processes underlying Alzheimer's disease (AD) are hypothesized to begin years to decades before clinical symptom onset, while individuals are still cognitively normal. Although many studies have examined the effect of biomarkers of a ... Full text Link to item Cite

The transcriptional landscape of age in human peripheral blood.

Journal Article Nat Commun · October 22, 2015 Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European an ... Full text Link to item Cite

Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early After Stroke in a Mouse Model.

Journal Article Stroke · October 2015 BACKGROUND AND PURPOSE: Data from both humans and animal models suggest that most recovery from motor impairment after stroke occurs in a sensitive period that lasts only weeks and is mediated, in part, by an increased responsiveness to training. Here, we ... Full text Link to item Cite

Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts.

Journal Article Neurobiol Aging · August 2015 Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 differe ... Full text Link to item Cite

Relationship of medial temporal lobe atrophy, APOE genotype, and cognitive reserve in preclinical Alzheimer's disease.

Journal Article Hum Brain Mapp · July 2015 This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the t ... Full text Link to item Cite

Network neurodegeneration in Alzheimer's disease via MRI based shape diffeomorphometry and high-field atlasing

Journal Article Frontiers in Bioengineering and Biotechnology · January 1, 2015 This paper examines MRI analysis of neurodegeneration in Alzheimer's Disease (AD) in a network of structures within the medial temporal lobe using diffeomorphometry methods coupled with high-field atlasing in which the entorhinal cortex is partitioned into ... Full text Cite

Mild cognitive impairment and asymptomatic Alzheimer disease subjects: equivalent β-amyloid and tau loads with divergent cognitive outcomes.

Journal Article J Neuropathol Exp Neurol · April 2014 Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of t ... Full text Link to item Cite

Personality and risk of Alzheimer's disease: new data and meta-analysis.

Journal Article Alzheimers Dement · March 2014 BACKGROUND: We examine whether broad factors and specific facets of personality are associated with increased risk of incident Alzheimer's disease (AD) in a long-run longitudinal study and a meta-analysis of published studies. METHODS: Participants (n = 16 ... Full text Link to item Cite

Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease.

Journal Article Neurosci Lett · January 13, 2014 The aging-suppressor gene klotho encodes a single-pass transmembrane protein that is predominantly secreted by the choroid plexus of the brain and in the kidney. Klotho-deficient mice develop multiple aging phenotypes, including impaired cognition. Klotho ... Full text Link to item Cite

Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.

Journal Article Neurobiol Aging · December 2013 The levels of β-amyloid (Aβ) and phosphorylated tau (p-tau), as measured in cerebrospinal fluid, have been associated with the risk of progressing from normal cognition to onset of clinical symptoms during preclinical Alzheimer's disease. We examined wheth ... Full text Link to item Cite

Changes in brain function occur years before the onset of cognitive impairment.

Journal Article J Neurosci · November 13, 2013 To develop targeted intervention strategies for the treatment of Alzheimer's disease, we first need to identify early markers of brain changes that occur before the onset of cognitive impairment. Here, we examine changes in resting-state brain function in ... Full text Link to item Cite

CSF biomarker changes precede symptom onset of mild cognitive impairment.

Journal Article Neurology · November 12, 2013 OBJECTIVE: This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive im ... Full text Link to item Cite

The diffeomorphometry of temporal lobe structures in preclinical Alzheimer's disease

Journal Article NeuroImage: Clinical · October 31, 2013 This paper examines morphometry of MRI biomarkers derived from the network of temporal lobe structures including the amygdala, entorhinal cortex and hippocampus in subjects with preclinical Alzheimer's disease (AD). Based on template-centered population an ... Full text Cite

Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging.

Journal Article Neurobiol Aging · October 2013 We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cogniti ... Full text Link to item Cite

Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore Longitudinal Study of Aging.

Journal Article JAMA Neurol · September 1, 2013 IMPORTANCE: Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in tho ... Full text Link to item Cite

Genome-wide association study of obsessive-compulsive disorder.

Journal Article Mol Psychiatry · July 2013 Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic v ... Full text Link to item Cite

Constrained selected reaction monitoring: quantification of selected post-translational modifications and protein isoforms.

Journal Article Methods · June 15, 2013 Selected reaction monitoring (SRM) is a mass spectrometry method that can target signature peptides to provide for the detection and quantitation of specific proteins in complex biological samples. When quantifying a protein, multiple peptides are generate ... Full text Link to item Cite

Personality and resilience to Alzheimer's disease neuropathology: a prospective autopsy study.

Journal Article Neurobiol Aging · April 2013 Alzheimer's disease (AD) neuropathology is found at autopsy in approximately 30% of cognitively normal older individuals. We examined whether personality traits are associated with such resilience to clinical dementia in individuals with AD neuropathology. ... Full text Link to item Cite

Apolipoprotein E ε4 allele interacts with sex and cognitive status to influence all-cause and cause-specific mortality in U.S. older adults.

Journal Article J Am Geriatr Soc · April 2013 OBJECTIVES: To confirm associations of apolipoprotein E (ApoE) ε4 carrier status, sex, and time-dependent cognitive status with mortality risk and to investigate these joint effects of these associations in a cohort of community-dwelling U.S. adults. DESIG ... Full text Link to item Cite

Medial premotor cortex shows a reduction in inhibitory markers and mediates recovery in a mouse model of focal stroke.

Journal Article Stroke · February 2013 BACKGROUND AND PURPOSE: Motor recovery after ischemic stroke in primary motor cortex is thought to occur in part through training-enhanced reorganization in undamaged premotor areas, enabled by reductions in cortical inhibition. Here we used a mouse model ... Full text Link to item Cite

Relationship of cognitive reserve and APOE status to the emergence of clinical symptoms in preclinical Alzheimer's disease.

Journal Article Cogn Neurosci · 2013 The APOE ε4 allele increases the risk of developing Alzheimer's disease, whereas the APOE ε2 allele reduces risk. We examined whether cognitive reserve (CR), as measured by an index consisting of education, reading, and vocabulary, modifies these associati ... Full text Link to item Cite

Carotid atherosclerosis and prospective risk of dementia.

Journal Article Stroke · December 2012 BACKGROUND AND PURPOSE: Although vascular risk factors have been implicated in the development of all-cause dementia and Alzheimer disease (AD), few studies have examined the association between subclinical atherosclerosis and prospective risk of dementia. ... Full text Link to item Cite

Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques.

Journal Article Acta Neuropathol · December 2012 The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investiga ... Full text Link to item Cite

Cerebral white matter disease is associated with Alzheimer pathology in a prospective cohort.

Journal Article Alzheimers Dement · October 2012 BACKGROUND: Although magnetic resonance imaging (MRI)-detected white matter disease has been correlated with cognitive decline in the elderly individuals, it is unclear whether white matter disease is primarily responsible for the cognitive deterioration o ... Full text Link to item Cite

Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain.

Journal Article Neurobiol Dis · July 2012 Genome-wide association studies have nominated many genetic variants for common human traits, including diseases, but in many cases the underlying biological reason for a trait association is unknown. Subsets of genetic polymorphisms show a statistical ass ... Full text Link to item Cite

Longitudinal brain activity changes in asymptomatic Alzheimer disease.

Journal Article Brain Behav · May 2012 Asymptomatic Alzheimer disease (ASYMAD) is characterized by normal cognition despite substantial AD pathology. To identify factors contributing to cognitive resilience, we compared early changes in regional cerebral blood flow (rCBF) in individuals subsequ ... Full text Link to item Cite

Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline.

Journal Article Neurobiol Aging · April 2012 We examined longitudinal associations between the apolipoprotein E ε4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex. Data on 644 non-Hispanic Caucasian adults, from the Baltimore Longitudinal Study of Aging ( ... Full text Link to item Cite

Cerebrospinal fluid Aβ and tau level fluctuation in an older clinical cohort.

Journal Article Arch Neurol · February 2012 OBJECTIVE: To determine whether cerebrospinal fluid (CSF) biomarkers for Alzheimer disease fluctuate significantly over time in a cohort of older, mildly symptomatic individuals. DESIGN: Biomarker validation in a clinical cohort. SETTING: University hospit ... Full text Link to item Cite

Con: Alzheimer's disease and circadian dysfunction: chicken or egg?

Journal Article Alzheimers Res Ther · 2012 The development of late-onset Alzheimer's disease is believed to be influenced by genetic, socioeconomic, and lifestyle factors. Recently, converging research in animal and human studies has found that beta-amyloid (Aβ) levels in cerebrospinal fluid are mo ... Full text Link to item Cite

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.

Journal Article Alzheimers Dement · July 2011 BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements betwe ... Full text Link to item Cite

Vascular dementia: atherosclerosis, cognition and Alzheimer's disease.

Journal Article Curr Alzheimer Res · June 2011 Both Alzheimer's disease type pathology (neuritic plaques and neurofibrillary tangles) and evidence of atherosclerosis and infarcts are common in autopsy specimens from the brains of patients enrolled in longitudinal prospective cohorts; the relative contr ... Full text Link to item Cite

Large quantities of Abeta peptide are constitutively released during amyloid precursor protein metabolism in vivo and in vitro.

Journal Article J Biol Chem · May 6, 2011 The metabolism of the amyloid precursor protein (APP) has been extensively investigated because its processing generates the amyloid-β-peptide (Aβ), which is a likely cause of Alzheimer disease. Much prior research has focused on APP processing using trans ... Full text Link to item Cite

In vivo fibrillar beta-amyloid detected using [11C]PiB positron emission tomography and neuropathologic assessment in older adults.

Journal Article Arch Neurol · February 2011 BACKGROUND: In demented older adults, in vivo amyloid imaging shows agreement with diagnostic neuropathologic assessment of β-amyloid (Aβ). However, the extent of agreement in nondemented older adults remains unclear. OBJECTIVE: To compare Aβ quantified us ... Full text Link to item Cite

Hearing loss and incident dementia.

Journal Article Arch Neurol · February 2011 OBJECTIVE: To determine whether hearing loss is associated with incident all-cause dementia and Alzheimer disease (AD). DESIGN: Prospective study of 639 individuals who underwent audiometric testing and were dementia free in 1990 to 1994. Hearing loss was ... Full text Link to item Cite

Amyloid precursor protein processing and Alzheimer's disease.

Journal Article Annu Rev Neurosci · 2011 Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, bioc ... Full text Link to item Cite

Cerebrospinal fluid profiles and prospective course and outcome in patients with amnestic mild cognitive impairment.

Journal Article Arch Neurol · January 2011 OBJECTIVES: To examine the effect of specific cerebrospinal fluid (CSF) profiles on the rate of cognitive decline, disease progression, and risk of conversion to Alzheimer disease (AD) dementia in patients with amnestic mild cognitive impairment (MCI). DES ... Full text Link to item Cite

Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing.

Journal Article Brain · August 2010 Recent studies suggest that dementia in the most elderly (90 years of age and above) is only modestly related to Alzheimer's disease pathology. This raises the possibility that other, as yet unknown, disease processes may underlie dementia in this rapidly ... Full text Link to item Cite

Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort.

Journal Article Ann Neurol · August 2010 OBJECTIVE: Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis ... Full text Link to item Cite

Neuropathologic studies of the Baltimore Longitudinal Study of Aging (BLSA).

Journal Article J Alzheimers Dis · 2009 The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The BLSA is supported by the National Institute of Aging (NIA) and its mission is to learn what happens to ... Full text Link to item Cite

Association of adiposity status and changes in early to mid-adulthood with incidence of Alzheimer's disease.

Journal Article Am J Epidemiol · November 15, 2008 Adiposity status and change are potential risk factors for Alzheimer's disease (AD). The authors used data on 2,322 participants in the Baltimore Longitudinal Study of Aging to analyze the relation between AD incidence and adiposity in Cox proportional haz ... Full text Link to item Cite

Effect of infarcts on dementia in the Baltimore longitudinal study of aging.

Journal Article Ann Neurol · August 2008 OBJECTIVE: To define the magnitude and mechanism of the effect of brain infarcts on the odds of dementia in a prospective study. METHODS: We examined the effects of brain infarcts and Alzheimer's disease (AD) pathology on the risk for dementia in 179 subje ... Full text Link to item Cite

Neuronal hypertrophy in asymptomatic Alzheimer disease.

Journal Article J Neuropathol Exp Neurol · June 2008 The pathologic changes of Alzheimer disease (AD) evolve very gradually over decades before the disease becomes clinically manifest. Thus, it is not uncommon to find substantial numbers of Abeta plaques and neurofibrillary tangles in autopsy brains of older ... Full text Link to item Cite

Morphometry of the human substantia nigra in ageing and Parkinson's disease.

Journal Article Acta Neuropathol · April 2008 To investigate the relation between the loss of substantia nigra (SN) neurons in normal ageing and Parkinson's disease (PD), we measured the total number and the cell body volume of pigmented (neuromelanin) neurons in the SN. We examined young (n = 7, mean ... Full text Link to item Cite

Resistance to Alzheimer's pathology is associated with nuclear hypertrophy in neurons.

Journal Article Neurobiol Aging · October 2007 This study focuses on the morphometric changes of neurons in asymptomatic Alzheimer's disease (AD), a state characterized by the presence of AD lesions in subjects without cognitive impairment. In autopsy brains, we used stereological methods to compare th ... Full text Link to item Cite

Reply from the authors [4]

Journal Article Neurology · May 1, 2007 Full text Cite

Activity dependent localization of synaptic NMDA receptors in spinal neurons.

Journal Article Mol Cell Neurosci · April 2007 In cultured spinal neurons, NMDA receptors are absent from excitatory synapses under basal conditions, but can be made to appear at excitatory synapses following blockade of excitatory synaptic activity. The activity dependent synaptic localization of NMDA ... Full text Link to item Cite

Rates of depression in individuals with pathologic but not clinical Alzheimer disease are lower than those in individuals without the disease: findings from the Baltimore Longitudinal Study on Aging (BLSA).

Journal Article Alzheimer Dis Assoc Disord · 2007 The prevalence of major depression is increased in Alzheimer disease (AD), but currently the basis of this association remains unclear. The present study examined rates of depression in 4 groups of participants with postmortem examination from the Baltimor ... Full text Link to item Cite

Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly.

Journal Article Ann Neurol · December 2006 OBJECTIVE: Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and with ... Full text Link to item Cite

Effect of a clinical stroke on the risk of dementia in a prospective cohort.

Journal Article Neurology · October 24, 2006 OBJECTIVE: To examine the risk and determinants of dementia following a clinically overt stroke in a prospectively followed cohort of elderly subjects. METHODS: We examined the effect of a clinically detectable stroke on the risk of dementia using prospect ... Full text Link to item Cite

Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA).

Journal Article J Neuropathol Exp Neurol · February 2005 Alpha-synuclein (alpha-synuclein) lesions are characteristic of idiopathic Parkinson disease (PD) and other alpha-synucleinopathies. To study the frequency of alpha-synuclein lesions in normal aging and how frequently they coexist with lesions of Alzheimer ... Full text Link to item Cite

Brief screening tests for the diagnosis of dementia: comparison with the mini-mental state exam.

Journal Article Alzheimer Dis Assoc Disord · 2005 Dementia is a common and under-diagnosed problem among the elderly. An accurate screening test would greatly aid the ability of physicians to evaluate dementia and memory problems in clinical practice. We sought to determine whether simple and brief psycho ... Full text Link to item Cite

AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by Stargazin and NR2A/B in spinal neurons and hippocampal interneurons.

Journal Article Neuron · October 14, 2004 Under standard conditions, cultured ventral spinal neurons cluster AMPA- but not NMDA-type glutamate receptors at excitatory synapses on their dendritic shafts in spite of abundant expression of the ubiquitous NMDA receptor subunit NR1. We demonstrate here ... Full text Link to item Cite

Neuronal pentraxin 1: a novel mediator of hypoxic-ischemic injury in neonatal brain.

Journal Article J Neurosci · April 28, 2004 Neonatal hypoxic-ischemic brain injury is a major cause of neurological disability and mortality. Its therapy will likely require a greater understanding of the discrete neurotoxic molecular mechanism(s) triggered by hypoxia-ischemia (HI). Here, we investi ... Full text Link to item Cite

LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein.

Journal Article Genomics · February 2004 The leucine zipper-, EF-hand-containing transmembrane protein 1 (LETM1) has recently been cloned in an attempt to identify genes deleted in Wolf-Hirschhorn syndrome (WHS), a microdeletion syndrome characterized by severe growth and mental retardation, hypo ... Full text Link to item Cite

Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity.

Journal Article Neuron · July 31, 2003 Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis. Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1. These proteins are covalently linked by disulfide bonds into highly organize ... Full text Link to item Cite

Differing mechanisms for glutamate receptor aggregation on dendritic spines and shafts in cultured hippocampal neurons.

Journal Article J Neurosci · September 1, 2002 We have explored the ability of axons from spinal and hippocampal neurons to aggregate NMDA- and AMPA-type glutamate receptors on each other as a way of exploring the molecular differences between their presynaptic elements. Spinal axons, which normally cl ... Full text Link to item Cite

Synaptically targeted narp plays an essential role in the aggregation of AMPA receptors at excitatory synapses in cultured spinal neurons.

Journal Article J Neurosci · June 1, 2002 Neuronal activity regulated pentraxin (Narp) has been implicated in the aggregation of AMPA-type glutamate receptors (GluR) at excitatory synapses. In the present paper, we examine the role of endogenous Narp in excitatory synapse formation by using novel, ... Full text Link to item Cite

Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases.

Journal Article Neurology · January 9, 2001 The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an ave ... Full text Link to item Cite

Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp.

Journal Article Neuron · June 1999 Narp (neuronal activity-regulated pentraxin) is a secreted immediate-early gene (IEG) regulated by synaptic activity in brain. In this study, we demonstrate that Narp possesses several properties that make it likely to play a key role in excitatory synapto ... Full text Link to item Cite

Autonomic and peripheral (sensorimotor) neuropathy in chronic liver disease: a clinical and electrophysiologic study.

Journal Article Hepatology · June 1999 Peripheral neuropathy has been reported in association with chronic liver disease. However, the precise incidence, severity and characteristics of neuropathy, and the relationship of neuropathy to different etiologies of liver disease have not been defined ... Full text Link to item Cite

Cultured motor neurons possess calcium-permeable AMPA/kainate receptors.

Journal Article Neuroreport · March 17, 1999 We examined the biology of AMPA/kainate-induced motor neuron degeneration using dissociated spinal cord cultures and motor neuron-specific antibodies which enable characterization of individual motor neurons in culture. Cobalt, which is thought to pass thr ... Full text Link to item Cite

Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons.

Journal Article Nat Neurosci · January 1999 Many excitatory synapses are thought to be postsynaptically 'silent', possessing functional NMDA but lacking functional AMPA glutamate receptors. The acquisition of AMPA receptors at silent synapses may be important in synaptic plasticity and neuronal deve ... Full text Link to item Cite

Activity-dependent modulation of synaptic AMPA receptor accumulation.

Journal Article Neuron · November 1998 Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured ... Full text Link to item Cite

Molecular mechanisms of glutamate receptor clustering at excitatory synapses.

Journal Article Curr Opin Neurobiol · June 1998 The targeting of AMPA- and NMDA-type glutamate receptors to synapses in the central nervous system is essential for efficient excitatory synaptic transmission. Recent studies have indicated that protein-protein interactions of these receptors with synaptic ... Full text Link to item Cite

Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments.

Journal Article J Neurosci · January 15, 1998 NMDA receptors are excitatory neurotransmitter receptors critical for synaptic plasticity and neuronal development in the mammalian brain. These receptors are found highly concentrated in the postsynaptic membrane of glutamatergic synapses. To investigate ... Full text Link to item Cite

Redistribution and stabilization of cell surface glutamate receptors during synapse formation.

Journal Article J Neurosci · October 1, 1997 Although the regulation of neurotransmitter receptors during synaptogenesis has been studied extensively at the neuromuscular junction, little is known about the control of excitatory neurotransmitter receptors during synapse formation in central neurons. ... Full text Link to item Cite

The development of excitatory synapses in cultured spinal neurons.

Journal Article J Neurosci · October 1, 1997 Immunohistochemical studies of synapses in the CNS have demonstrated that glutamate receptors (GluRs) are concentrated at postsynaptic sites in vivo and in vitro (Baude et al., 1995). The mechanisms leading to receptor clustering at excitatory synapses are ... Full text Link to item Cite

GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors.

Journal Article Nature · March 20, 1997 AMPA glutamate receptors mediate the majority of rapid excitatory synaptic transmission in the central nervous system and play a role in the synaptic plasticity underlying learning and memory. AMPA receptors are heteromeric complexes of four homologous sub ... Full text Link to item Cite

Homer: a protein that selectively binds metabotropic glutamate receptors.

Journal Article Nature · March 20, 1997 Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotro ... Full text Link to item Cite

Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit.

Journal Article Neuron · June 1996 We have characterized the phosphorylation of the glutamate receptor subunit GluR1, using biochemical and electrophysiological techniques. GluR1 is phosphorylated on multiple sites that are all located on the C-terminus of the protein. Cyclic AMP-dependent ... Full text Link to item Cite

Isolation of embryonic chick motoneurons and their survival in vitro.

Journal Article J Neurosci · November 1986 This is the first of a series of 4 papers in which we describe the regulation of excitatory amino acid receptors on embryonic chick motoneurons dissociated from the lateral motor column and maintained in cell culture. Techniques are described for labeling ... Full text Link to item Cite

Excitatory synaptic transmission between interneurons and motoneurons in chick spinal cord cell cultures.

Journal Article J Neurosci · November 1986 We have examined the development of synaptic transmission between interneurons and motoneurons in spinal cord cell cultures. Unitary excitatory synaptic currents and complex bursts of excitatory currents develop rapidly: EPSCs (excitatory postsynaptic curr ... Full text Link to item Cite

Modulation of embryonic chick motoneuron glutamate sensitivity by interneurons and agonists.

Journal Article J Neurosci · November 1986 Embryonic chick motoneurons grown in culture together with other spinal cord cells are more sensitive to L-glutamate than are sorted motoneurons grown in isolation. After 6 d in vitro, the difference in peak sensitivity reached 6-fold. Comparable increases ... Full text Link to item Cite

Characterization of excitatory amino acid receptors expressed by embryonic chick motoneurons in vitro.

Journal Article J Neurosci · November 1986 We have examined the effect of L-glutamate and other excitatory amino acids on embryonic chick motoneurons maintained in cell culture along with other types of spinal cord cells. When the motoneuron membrane is clamped at -50 mV, glutamate induces a dose-d ... Full text Link to item Cite

The mechanism of action of ethanolamine ammonia-lyase, an adenosylcobalamin-dependent enzyme. Evidence that the hydrogen transfer mechanism involves a second intermediate hydrogen carrier in addition to the cofactor.

Journal Article J Biol Chem · December 25, 1985 Ethanolamine ammonia-lyase catalyzes the adenosylcobalamin (AdoCbl)-dependent conversion of ethanolamine to acetaldehyde and ammonia. During this reaction, a hydrogen atom migrates from the carbinol carbon of ethanolamine to the methyl carbon of acetaldehy ... Link to item Cite

On the mechanism of acetylcholine receptor accumulation at newly formed synapses on chick myotubes.

Journal Article J Neurosci · August 1985 We have examined the specificity and the mechanism of acetylcholine receptor (AChR) accumulation at embryonic chick nerve-muscle contacts that form in culture. Spinal cord motoneurons were identified in vitro after labeling them in vivo with Lucifer Yellow ... Full text Link to item Cite

The third component of complement: covalent attachment of a radioactive sugar to the labile binding site of C3 via the alternative pathway.

Journal Article J Immunol · June 1981 A complement- (C) fixing particle consisting of agarose beads to which 5-thioglucose was attached by a --S--S-- bond (agarose-thioglucose) was employed to investigate the mechanism of attachment of C3 to surfaces. When whole serum containing [125I] C3 was ... Link to item Cite