Scholars@Duke
Ornit Chiba-Falek

Ornit Chiba-Falek

Professor in Neurology
Neurology, Behavioral Neurology
o.chibafalek@duke.edu
Duke Box 2900, Durham, NC 27710
311 Research Drive, Bryan Research Building, Room 201A, Durham, NC 27710

Selected Publications

Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

Journal Article Alzheimers Dement · September 2024 INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid ... Full text Link to item Cite

Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.

Journal Article Acta Neuropathol Commun · July 2, 2024 The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precisi ... Full text Link to item Cite

Neuronal-type-specific epigenome editing to decrease SNCA expression: Implications for precision medicine in synucleinopathies.

Journal Article Mol Ther Nucleic Acids · March 12, 2024 Overexpression of SNCA has been implicated in the pathogenesis of synucleinopathies, particularly Parkinson's disease (PD) and dementia with Lewy bodies (DLB). While PD and DLB share some clinical and pathological similarities, each disease presents distin ... Full text Link to item Cite

Editorial: Amplifying Efficiency and Accuracy in Dementia Drug Development.

Journal Article The journal of prevention of Alzheimer's disease · January 2024 Full text Cite

Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer's disease brains.

Journal Article Cell Biosci · October 3, 2023 BACKGROUND: The genetic underpinnings of late-onset Alzheimer's disease (LOAD) are yet to be fully elucidated. Although numerous LOAD-associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain i ... Full text Link to item Cite

Bioinformatics pipeline to guide post-GWAS studies in Alzheimer's: A new catalogue of disease candidate short structural variants.

Journal Article Alzheimers Dement · September 2023 BACKGROUND: Short structural variants (SSVs), including insertions/deletions (indels), are common in the human genome and impact disease risk. The role of SSVs in late-onset Alzheimer's disease (LOAD) has been understudied. In this study, we developed a bi ... Full text Link to item Cite

The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression.

Journal Article J Alzheimers Dis · 2023 BACKGROUND: The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer's disease (LOAD) and other age-related conditions. OBJECTIVE: Here we developed the first humanized mouse model ... Full text Link to item Cite

Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients.

Journal Article Biomolecules · November 12, 2022 Depression is common among late-onset Alzheimer's Disease (LOAD) patients. Only a few studies investigated the genetic variability underlying the comorbidity of depression in LOAD. Moreover, the epigenetic and transcriptomic factors that may contribute to ... Full text Link to item Cite

Infection and inflammation: New perspectives on Alzheimer's disease.

Journal Article Brain Behav Immun Health · July 2022 Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ... Full text Link to item Cite

Bioinformatics pipeline to guide late-onset Alzheimer's disease (LOAD) post-GWAS studies: Prioritizing transcription regulatory variants within LOAD-associated regions.

Journal Article Alzheimers Dement (N Y) · 2022 INTRODUCTION: As new late-onset Alzheimer's disease (LOAD) genetic risk loci are identified and brain cell-type specific omics data becomes available, there is an unmet need for a bioinformatics framework to prioritize genes and variants for testing in sin ... Full text Link to item Cite

Polygenic Risk Score Effectively Predicts Depression Onset in Alzheimer's Disease Based on Major Depressive Disorder Risk Variants.

Journal Article Front Neurosci · 2022 INTRODUCTION: Depression is a common, though heterogenous, comorbidity in late-onset Alzheimer's Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiolog ... Full text Open Access Link to item Cite

Parallel single-nucleus chromatin accessibility and transcriptomic profiling of human late-onset Alzheimer's disease brains

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: In the post-GWAS era for late-onset Alzheimer's disease (LOAD), the precise disease-causing genes, the specific causal variants, and molecular mechanisms mediating their pathogenic effects remain unknown. Recent studies using single-nucleus (sn ... Full text Cite

Bioinformatics pipeline to advance the identification of transcription regulatory variants in LOAD noncoding regions

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: As new LOAD genetic risk loci are identified and more brain cell-type specific omics data becomes available, there is an unmet need for a bioinformatics framework to prioritize genes and variants for testing in single-cell molecular profiling e ... Full text Cite

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Journal Article Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · September 2021 Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerg ... Full text Cite

Polygenic Risk Score Effectively Predicts Risk of Depression Onset in Alzheimer’s Disease

Journal Article · August 27, 2021 AbstractIntroduction: Depression is a common, though heterogenous, comorbidity in late-onset Alzheimer’s Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In pre ... Full text Cite

Sex dependent glial-specific changes in the chromatin accessibility landscape in late-onset Alzheimer's disease brains.

Journal Article Mol Neurodegener · August 24, 2021 BACKGROUND: In the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer's disease (LOAD) and translate the associations to causation. METHODS: We conducted ATAC-seq profiling using NeuN sorted-nuclei f ... Full text Link to item Cite

The Path to Progress Preclinical Studies of Age-Related Neurodegenerative Diseases: A Perspective on Rodent and hiPSC-Derived Models.

Journal Article Mol Ther · March 3, 2021 Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent age-related neurodegenerative diseases, and currently no effective clinical treatments exist for either, despite decades of clinical trials. The failure to translate preclinic ... Full text Link to item Cite

APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer's.

Journal Article Int J Mol Sci · January 27, 2021 Alzheimer's disease (AD) has a critical unmet medical need. The consensus around the amyloid cascade hypothesis has been guiding pre-clinical and clinical research to focus mainly on targeting beta-amyloid for treating AD. Nevertheless, the vast majority o ... Full text Link to item Cite

Cell-Type Specific Changes in DNA Methylation of SNCA Intron 1 in Synucleinopathy Brains.

Journal Article Front Neurosci · 2021 Parkinson's disease (PD) and dementia with Lewy body (DLB) are the most common synucleinopathies. SNCA gene is a major genetic risk factor for these diseases group, and dysregulation of its expression has been implicated in the genetic etiologies of severa ... Full text Link to item Cite

Lentiviral vectors as the delivery vehicles for transduction into iPSCs: Shortcomings and benefits

Chapter · January 1, 2021 Over the last decade, the generation and differentiation of induced pluripotent stem cells (iPSCs) from somatic cells highlights one of the most groundbreaking discoveries in science and medicine. iPSCs has become an indispensable tool for elucidating a pa ... Full text Cite

The mechanistic role of alpha-synuclein in the nucleus: impaired nuclear function caused by familial Parkinson's disease SNCA mutations.

Journal Article Hum Mol Genet · November 4, 2020 Alpha-synuclein SNCA has been implicated in the etiology of Parkinson's disease (PD); however, the normal function of alpha-synuclein protein and the pathway that mediates its pathogenic effect is yet to be discovered. We investigated the mechanistic role ... Full text Link to item Cite

Good problems to have? Policy and societal implications of a disease-modifying therapy for presymptomatic late-onset Alzheimer's disease.

Journal Article Life Sci Soc Policy · October 12, 2020 In the United States alone, the prevalence of AD is expected to more than double from six million people in 2019 to nearly 14 million people in 2050. Meanwhile, the track record for developing treatments for AD has been marked by decades of failure. But re ... Full text Link to item Cite

Shared genetic etiology underlying late-onset Alzheimer's disease and posttraumatic stress syndrome.

Journal Article Alzheimers Dement · September 2020 INTRODUCTION: Late-onset Alzheimer's disease (LOAD) manifests comorbid neuropsychiatric symptoms and posttraumatic stress disorder (PTSD) is associated with an increased risk for dementia in late life, suggesting the two disorders may share genetic etiolog ... Full text Open Access Link to item Cite

Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders.

Journal Article Dis Model Mech · August 27, 2020 The importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk an ... Full text Link to item Cite

Shared genetic etiology underlying Alzheimer's disease and major depressive disorder.

Journal Article Transl Psychiatry · March 9, 2020 Patients with late-onset Alzheimer's disease (LOAD) frequently manifest comorbid neuropsychiatric symptoms with depression and anxiety being most frequent, and individuals with major depressive disorder (MDD) have an increased prevalence of LOAD. This sugg ... Full text Link to item Cite

Implications of Gene Therapy for Alzheimer's

Conference MOLECULAR THERAPY · 2020 Cite

Gene-Editing Technologies Paired With Viral Vectors for Translational Research Into Neurodegenerative Diseases.

Journal Article Front Mol Neurosci · 2020 Diseases of the central nervous system (CNS) have historically been among the most difficult to treat using conventional pharmacological approaches. This is due to a confluence of factors, including the limited regenerative capacity and overall complexity ... Full text Link to item Cite

Bioinformatics strategy to advance the interpretation of Alzheimer's disease GWAS discoveries: The roads from association to causation.

Journal Article Alzheimers Dement · August 2019 INTRODUCTION: Genome-wide association studies (GWAS) discovered multiple late-onset Alzheimer's disease (LOAD)-associated SNPs and inferred the genes based on proximity; however, the actual causal genes are yet to be identified. METHODS: We defined LOAD-GW ... Full text Link to item Cite

Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

Journal Article Am J Hum Genet · August 1, 2019 Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational ... Full text Link to item Cite

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Journal Article Nat Commun · May 1, 2019 Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article. ... Full text Link to item Cite

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models.

Journal Article J Vis Exp · March 29, 2019 The use of hiPSC-derived cells represents a valuable approach to study human neurodegenerative diseases. Here, we describe an optimized protocol for the differentiation of hiPSCs derived from a patient with the triplication of the alpha-synuclein gene (SNC ... Full text Link to item Cite

Multiplication of the SNCA locus exacerbates neuronal nuclear aging.

Journal Article Hum Mol Genet · February 1, 2019 Human-induced Pluripotent Stem Cell (hiPSC)-derived models have advanced the study of neurodegenerative diseases, including Parkinson's disease (PD). While age is the strongest risk factor for these disorders, hiPSC-derived models represent rejuvenated neu ... Full text Link to item Cite

The Landscape of SNCA Transcripts Across Synucleinopathies: New Insights From Long Reads Sequencing Analysis.

Journal Article Front Genet · 2019 Dysregulation of alpha-synuclein expression has been implicated in the pathogenesis of synucleinopathies, in particular Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Previous studies have shown that the alternatively spliced isoforms of the ... Full text Link to item Cite

Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD.

Journal Article Mol Ther · November 7, 2018 Elevated levels of SNCA have been implicated in the pathogenesis of Parkinson's disease (PD), while normal physiological levels of SNCA are needed to maintain neuronal function. We ought to develop new therapeutic strategies targeting the regulation of SNC ... Full text Link to item Cite

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

Journal Article Twin Res Hum Genet · October 2018 Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Tar ... Full text Link to item Cite

Toward deciphering the mechanistic role of variations in the Rep1 repeat site in the transcription regulation of SNCA gene.

Journal Article Neurogenetics · August 2018 Short structural variants-variants other than single nucleotide polymorphisms-are hypothesized to contribute to many complex diseases, possibly by modulating gene expression. However, the molecular mechanisms by which noncoding short structural variants ex ... Full text Link to item Cite

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Journal Article Nat Genet · July 2018 Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be disco ... Full text Link to item Cite

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Journal Article Nat Commun · May 29, 2018 General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and ... Full text Link to item Cite

The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.

Journal Article Alzheimers Dement · May 2018 The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in linkage disequilibrium with APOE. Roses et al. identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzhe ... Full text Link to item Cite

Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes.

Journal Article PLoS One · 2018 Peroxisome proliferator-activated receptor-γ (PPARγ), is a transcription factor that governs pathways, such as lipid metabolism and immune response, that have been implicated in the etiology of LOAD. Previously, we established HepG2-derived cell-lines with ... Full text Link to item Cite

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.

Journal Article Cell Rep · November 28, 2017 Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated wi ... Full text Link to item Cite

Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies.

Journal Article Alzheimers Dement · November 2017 INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding s ... Full text Link to item Cite

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

Journal Article Mol Psychiatry · November 2017 This corrects the article DOI: 10.1038/mp.2016.244. ... Full text Link to item Cite

Structural variants in SNCA gene and the implication to synucleinopathies.

Journal Article Curr Opin Genet Dev · June 2017 Synucleinopathies are a group of neurodegenerative diseases that share a common pathological lesion of intracellular protein inclusions largely composed of aggregates of alpha-synuclein protein. Accumulating evidence, including genome-wide association stud ... Full text Link to item Cite

The effects of PPARγ on the regulation of the TOMM40-APOE-C1 genes cluster.

Journal Article Biochim Biophys Acta Mol Basis Dis · March 2017 Chromosome 19q13.32 is a gene rich region, and has been implicated in multiple human phenotypes in adulthood including lipids traits, Alzheimer's disease, and longevity. Peroxisome Proliferator Activated Receptor Gamma (PPARγ) is a ligand-activated nuclear ... Full text Link to item Cite

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

Journal Article Mol Psychiatry · March 2017 The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GW ... Full text Link to item Cite

Interpreting Gene Expression Effects of Disease-Associated Variants: A Lesson from SNCA rs356168.

Journal Article Front Genet · 2017 The SNCA intronic single nucleotide polymorphism (SNP), rs356168, has been associated with Parkinson's disease (PD) in large genome wide association studies (GWAS). Recently, the PD-risk allele, rs356168-G was shown to increase SNCA-mRNA expression using g ... Full text Link to item Cite

Towards precision medicine in Alzheimer's disease: deciphering genetic data to establish informative biomarkers.

Journal Article Expert Rev Precis Med Drug Dev · 2017 INTRODUCTION: Developing biomarker tools for identification of individuals at high-risk for late-onset Alzheimer's disease (LOAD) is important for prognosis and early treatment. This review focuses on genetic factors and their potential role for precision ... Full text Link to item Cite

The SSV Evaluation System: A Tool to Prioritize Short Structural Variants for Studies of Possible Regulatory and Causal Variants.

Journal Article Hum Mutat · September 2016 Short structural variants (SSVs) are short genomic variants (<50 bp) other than SNPs. It has been suggested that SSVs contribute to many human complex traits. However, high-throughput analysis of SSVs presents numerous technical challenges. In order to fac ... Full text Link to item Cite

Up-regulation of SNCA gene expression: implications to synucleinopathies.

Journal Article Neurogenetics · July 2016 Synucleinopathies are a group of neurodegenerative diseases that share a common pathological lesion of intracellular protein inclusions largely composed by aggregates of alpha-synuclein protein. Accumulating evidence, including genome wide association stud ... Full text Link to item Cite

The Role of Upregulated APOE in Alzheimer's Disease Etiology.

Journal Article J Alzheimers Dis Parkinsonism · March 2016 Full text Link to item Cite

Structural variants can be more informative for disease diagnostics, prognostics and translation than current SNP mapping and exon sequencing.

Journal Article Expert Opin Drug Metab Toxicol · 2016 INTRODUCTION: In this article we discuss several human neurological diseases and their relationship to specific highly polymorphic small structural variants (SVs). Unlike genome-wide association analysis (GWAS), this methodology is not a genome screen to d ... Full text Link to item Cite

Gene Expression Analysis of Neurons and Astrocytes Isolated by Laser Capture Microdissection from Frozen Human Brain Tissues.

Journal Article Front Mol Neurosci · 2016 Different cell types and multiple cellular connections characterize the human brain. Gene expression analysis using a specific population of cells is more accurate than conducting analysis of the whole tissue homogenate, particularly in the context of neur ... Full text Link to item Cite

A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression.

Journal Article Alzheimers Dement · October 2015 INTRODUCTION: We recently showed that tagging single-nucleotide polymorphisms across the SNCA locus were significantly associated with increased risk for Lewy body (LB) pathology in Alzheimer's disease (AD) cases. However, the actual genetic variant(s) tha ... Full text Link to item Cite

African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles.

Journal Article Alzheimers Dement · November 2014 BACKGROUND: Several studies have demonstrated a lower apolipoprotein E4 (APOE ε4) allele frequency in African-Americans, but yet an increased age-related prevalence of AD. An algorithm for prevention clinical trials incorporating TOMM40'523 (Translocase of ... Full text Link to item Cite

The Broad Impact of TOM40 on Neurodegenerative Diseases in Aging.

Journal Article J Parkinsons Dis Alzheimers Dis · November 2014 Mitochondrial dysfunction is an important factor in the pathogenesis of age-related diseases, including neurodegenerative diseases like Alzheimer's and Parkinson's spectrum disorders. A polymorphism in Translocase of the Outer Mitochondrial Membrane - 40 k ... Full text Link to item Cite

The genetic contributions of SNCA and LRRK2 genes to Lewy Body pathology in Alzheimer's disease.

Journal Article Hum Mol Genet · September 15, 2014 The molecular genetic basis that leads to Lewy Body (LB) pathology in 15-20% of Alzheimer disease cases (LBV/AD) was largely unknown. Alpha-synuclein (SNCA) and Leucine-rich repeat kinase2 (LRRK2) have been implicated in the pathogenesis of Parkinson's dis ... 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

Glucocerebrosidase gene mutations associated with Parkinson's disease: a meta-analysis in a Chinese population.

Journal Article PLoS One · 2014 Mutations of glucocerebrosidase (GBA) confer susceptibility to Parkinson's disease in several ethnical populations, with a high incidence especially in the Ashkenazi Jewish population. Although there are several studies that have investigated a similar ass ... Full text Link to item Cite

A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.

Journal Article Mol Psychiatry · January 2014 Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual differences in nonpathological cognitive ageing in five coho ... 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

Clinical Trials of AD Delay of Onset: Enrichment by a Prognostic Genetic Biomarker

Book · January 1, 2013 Modern medicine is shifting its focus to predictive and preventive healthcare utilization. To support this change, early intervention clinical trials that delay the onset of symptomatic disease must be conducted in a safe and cost-effective manner, and wit ... Full text Cite

A comparison of the Cambridge Automated Neuropsychological Test Battery (CANTAB) with "traditional" neuropsychological testing instruments.

Journal Article J Clin Exp Neuropsychol · 2013 The Cambridge Neuropsychological Test Automated Battery (CANTAB) is frequently used in research protocols and increasingly in clinical practice. Despite the frequency of its use, important aspects of its measurement validity have yet to be established in h ... Full text Link to item Cite

Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.

Journal Article Hum Genet · December 2012 Hepatitis C virus (HCV) modulates host lipid metabolism as part of its lifecycle and is dependent upon VLDL for co-assembly and secretion. HCV dyslipidemia is associated with steatosis, insulin resistance, IL28B genotype and disease progression. Apolipopro ... Full text Link to item Cite

A homopolymer polymorphism in the TOMM40 gene contributes to cognitive performance in aging.

Journal Article Alzheimers Dement · September 2012 INTRODUCTION: A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset. OBJECTIVE: To explore the effects of the polymorphic polyT tract (rs10524523, referred as '523') on cognitive pe ... 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

Characterization of the poly-T variant in the TOMM40 gene in diverse populations.

Journal Article PLoS One · 2012 We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimer's disease and with cognitive performance in elderly. Three allele groups were defined f ... Full text Link to item Cite

Contribution of pastimes and testing strategies to the performance of healthy volunteers on cognitive tests.

Journal Article Clin Neuropsychol · July 2011 Clinicians routinely query factors known to impact cognitive test scores, including age and education. However, without data delineating the impact of less-frequently tracked variables, clinicians are limited to educated inferences about their effect. We e ... 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

Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study.

Journal Article BMC Med Genet · January 19, 2010 BACKGROUND: Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex ... Full text Open Access Link to item Cite

Sex-specific effects of scavenger receptor class B type 1 (SR-BI) gene variants on serum lipid levels and hepatic gene expression.

Journal Article BMC medical genetics · January 2010 ABSTRACT: BACKGROUND: Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this ge ... Cite

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

Journal Article J Alzheimers Dis · 2010 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

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

Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain.

Journal Article Hum Mol Genet · September 1, 2009 Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). Recently, it was shown that an increase in SNCA copy numbers leads to elevated levels of wild-type SNCA-mRNA and protein and is sufficient ... Full text Link to item Cite

Reply: Expression of α-synuclein mRNA in Parkinson's disease [3]

Journal Article Movement Disorders · May 15, 2007 Full text Cite

Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients.

Journal Article Mov Disord · October 2006 Lewy bodies, the pathological hallmark of Parkinson's disease (PD), consist largely of alpha-synuclein, a 14.5-kDa presynaptic neuronal protein implicated in familial PD. An increased copy number and elevated expression of wild-type alpha-synuclein (SNCA) ... Full text Link to item Cite

Regulation of alpha-synuclein expression by poly (ADP ribose) polymerase-1 (PARP-1) binding to the NACP-Rep1 polymorphic site upstream of the SNCA gene.

Journal Article Am J Hum Genet · March 2005 Alleles at NACP-Rep1, the polymorphic microsatellite repeat located approximately 10 kb upstream of the alpha -synuclein gene (SNCA), are associated, in some reports, with differing risks of sporadic Parkinson disease (PD). We showed previously that NACP-R ... Full text Link to item Cite

Restoration of the cystic fibrosis transmembrane conductance regulator function by splicing modulation.

Journal Article EMBO Rep · November 2004 A significant fraction of disease-causing mutations affects pre-mRNA splicing. These mutations can generate both aberrant and correct transcripts, the level of which varies among different patients. An inverse correlation was found between this level and d ... Full text Link to item Cite

Functional analysis of intra-allelic variation at NACP-Rep1 in the alpha-synuclein gene.

Journal Article Hum Genet · October 2003 NACP-Rep1, a polymorphic microsatellite upstream of the alpha-synuclein gene ( SNCA), consisting of the nucleotides (TC)(x)(T)(2)(TC)(y)(TA)(z)(CA)(w), has five alleles originally defined by 2-bp differences in (CA)(w). Different NACP-Rep1 alleles have bee ... Full text Link to item Cite

Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system.

Journal Article Hum Mol Genet · December 15, 2001 Mutations in the alpha-synuclein gene (SNCA) have been implicated in familial Parkinson's disease (PD) while certain polymorphic alleles at a microsatellite repeat, NACP-Rep1, located approximately 10 kb upstream of the gene, have been associated with spor ... Full text Link to item Cite

Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element.

Journal Article Genome Res · January 2001 The human alpha-synuclein gene (SNCA) encodes a presynaptic nerve terminal protein that was originally identified as a precursor of the non-beta-amyloid component of Alzheimer's disease plaques. More recently, mutations in SNCA have been identified in some ... Full text Link to item Cite

Analysis of the human alpha-synuclein promoter.

Journal Article AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 2000 Link to item Cite

Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations.

Journal Article Hum Mol Genet · July 22, 2000 Variable levels of aberrantly spliced cystic fibrosis transmembrane conductance regulator (CFTR ) transcripts were suggested to correlate with variable cystic fibrosis (CF) severity. We studied the effect of the cellular splicing factors, hnRNP A1 and ASF/ ... Full text Link to item Cite

Variable levels of normal RNA in different fetal organs carrying a cystic fibrosis transmembrane conductance regulator splicing mutation.

Journal Article Am J Respir Crit Care Med · June 1999 Disease severity varies among cystic fibrosis (CF) patients carrying the same cystic fibrosis transmembrane conductance regulator (CFTR) genotype and among organs of the same individual. It has been shown that the class V splicing mutation 3849 + 10 kb C-- ... Full text Link to item Cite

The molecular basis of disease variability among cystic fibrosis patients carrying the 3849+10 kb C-->T mutation.

Journal Article Genomics · November 1, 1998 Disease severity varies among cystic fibrosis (CF) patients carrying the same CFTR genotype. Here we studied the mechanism underlying disease variability in individuals carrying a splicing CFTR mutation, 3849+10 kb C-->T. This mutation was shown to produce ... Full text Link to item Cite

Screening of CFTR mutations in an isolated population: identification of carriers and patients.

Journal Article Eur J Hum Genet · 1998 One important application of the identification of disease-causing mutations is carrier screening in the general population. Such a project requires a simple accurate test by which a large proportion of the mutations can be identified. This study describes ... Full text Link to item Cite

A cystic fibrosis transmembrane conductance regulator splice variant with partial penetrance associated with variable cystic fibrosis presentations.

Journal Article Am J Respir Crit Care Med · June 1997 Some patients express various features of cystic fibrosis (CF) even though essential characteristics of the disease might be absent. Such patients may suffer from respiratory disease without pancreatic insufficiency and normal sweat chloride levels. Others ... Full text Link to item Cite

Cystic fibrosis in Jews: frequency and mutation distribution.

Journal Article Genet Test · 1997 The incidence of cystic fibrosis and the frequency of disease causing mutations varies among different ethnic groups and geographical regions around the world. The Jewish population is comprised of two major ethnic groups. Ashkenazi and Non-Ashkenazi. The ... Full text Link to item Cite

CFTR haplotype analysis reveals genetic heterogeneity in the etiology of congenital bilateral aplasia of the vas deferens.

Journal Article Am J Hum Genet · June 1995 Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in males with CBAVD revealed that in some males CBAVD ... Link to item Cite