ArticleHuman molecular genetics2014
Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
Open access · greenAbstract readMulticenter Study
In one paragraph
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 1 of them a synthesis that pooled it.
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150citing papers in PubMed, 1 pooled it
16.5field-weighted citation impact, top 1% of its field
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Who cites it
150 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Effect of GBA gene variants on clinical characteristics of dementia with Lewy bodies: a review and meta-analyses.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Pooled it
- Review
- Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study.NPJ Parkinson's disease · 2026Article
- Identification of KHS-101 as a Transcription Factor EB Activator to Promote α-Synuclein Degradation.International journal of molecular sciences · 2026Article
- Meta-analysis reveals apolipoprotein ε4 confers higher susceptibility to Parkinson's disease dementia in Asian populations.Frontiers in aging neuroscience · 2026Article
- Interplay Between 3D Chromatin Architecture and Gene Regulation at theInternational journal of molecular sciences · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- The mechanisms underlying TDP-43-associated neurodegeneration in Alzheimer's disease and related dementias.Molecular psychiatry · 2025Review
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein.Molecular neurodegeneration · 2025Review
- Comorbid Pathologies and Their Impact on Dementia with Lewy Bodies-Current View.International journal of molecular sciences · 2025Review
- Age-dependent interactions of APOE isoform 4 and Alzheimer's disease neuropathology: findings from the NACC.Acta neuropathologica communications · 2025Article
- Genetic risk and plasma biomarkers of dementia with Lewy bodies in a Chinese population.NPJ Parkinson's disease · 2025Article
- Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- A genome-wide association study identifies a novel East Asian-specific locus for dementia with Lewy bodies in Japanese subjects.Molecular medicine (Cambridge, Mass.) · 2025Article
- Regulation of CNS Lipids by Protease Activated Receptor 1.Journal of neurochemistry · 2025Article
- Exercise as a multitarget therapy: modulating myokines, neurotrophins, and inflammation in Parkinson's disease.Frontiers in aging neuroscience · 2025Review
- The role ofFrontiers in neuroscience · 2025Review
90 more citing papers are in PubMed but not listed here.
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Authors and funding
42 authors at 20 institutions in 9 countries.
Jose BrasDepartment of Molecular Neuroscience, j.bras@ucl.ac.uk.
Rita GuerreiroDepartment of Molecular Neuroscience.
Lee DarwentDepartment of Molecular Neuroscience.
Laura ParkkinenNuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Olaf AnsorgeNuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Valentina Escott-PriceMRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Dena G HernandezLaboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, USA.
Michael A NallsLaboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, USA.
Lorraine N ClarkTaub Institute for Alzheimer Disease and the Aging Brain, Department of Pathology and Cell Biology, and.
Lawrence S HonigTaub Institute for Alzheimer Disease and the Aging Brain, Department of Neurology, Columbia University, New York, NY, USA.
Karen MarderTaub Institute for Alzheimer Disease and the Aging Brain, Department of Neurology, Columbia University, New York, NY, USA.
Wiesje M Van Der FlierDepartment of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Afina LemstraDepartment of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Philip ScheltensDepartment of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Ekaterina RogaevaDepartment of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Peter St George-HyslopDepartment of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada, Cambridge Institute for Medical Research, and Cambridge National Institute of Health Research Biomedical Research Unit in Dementia, University of Cambridge, Cambridge CB2 0XY, UK.
Elisabet LondosClinical Memory Research Unit, Institute Clinical Sciences Malmö, Lund University, Sweden.
Henrik ZetterbergDepartment of Molecular Neuroscience, Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Sara Ortega-CuberoNeurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain, Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain, CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
Pau PastorNeurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain, Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain, CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
Tanis J FermanDepartment of Psychiatry, Department of Psychology.
Neill R Graff-RadfordDepartment of Neurology and.
Owen A RossDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Imelda BarberTranslation Cell Sciences - Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Anne BraaeTranslation Cell Sciences - Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Kristelle BrownTranslation Cell Sciences - Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Kevin MorganTranslation Cell Sciences - Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Walter MaetzlerHertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, and DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Germany.
Daniela BergHertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, and DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Germany.
Claire TroakesMRC London Neurodegenerative Diseases Brain Bank, Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
Safa Al-SarrajMRC London Neurodegenerative Diseases Brain Bank, Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
Tammaryn LashleyQueen Square Brain Bank, Department of Molecular Neuroscience, and.
Yaroslau ComptaQueen Square Brain Bank, Department of Molecular Neuroscience, and Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, Barcelona, Catalonia, Spain.
Tamas ReveszQueen Square Brain Bank, Department of Molecular Neuroscience, and.
Andrew LeesQueen Square Brain Bank, Department of Molecular Neuroscience, and.
Nigel CairnsKnight Alzheimer's Disease Research Center and Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
Glenda M HallidayNeuroscience Research Australia, Sydney, Australia, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
David MannInstitute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and.
Stuart Pickering-BrownInstitute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Andrew SingletonLaboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, USA.
John HardyReta Lila Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
Laboratory of Molecular Genetics · PLNational Institute on Aging · USUniversity of Nottingham · GBAmsterdam UMC Location VUmc · NLColumbia University · USKing's College London · GBMayo Clinic in Florida · USUniversity of Oxford · GBAmsterdam Neuroscience · NLBiomedical Research Networking Center on Neurodegenerative Diseases · ESCardiff University · GBConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESGerman Center for Neurodegenerative Diseases · DEHertie Institute for Clinical Brain Research · DEInstituto de Salud Carlos III · ESLund University · SENational Institute for Health Research · GBNeuroscience Research Australia · AUQueen's Medical Centre · GBUniversity College London · GB
Funding
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MTRANSLATIONAL APPROACHES TO NEUROPROTECTION OF AXONS IN PDrP50NS038370 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BURKE, ROBERT E · 1999 to 2014
$24.0MAssessment of Candidate Loci in Neurological diseasesZIAAG000957 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$12.2MNeuropathology CoreP50NS072187 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2010 to 2017
$8.7MGenetic Analysis Of Alzheimer s DiseaseZIAAG000950 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2019
$6.9MGenetic Analysis Of Non- Alzheimer's disease DementiasZIAAG000951 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2020
$5.6MUnderstanding the role of MAPT in Parkinsonian disordersR01NS078086 · NINDS · MAYO CLINIC JACKSONVILLE · PI ROSS, OWEN A · 2012 to 2016
$1.7MMolecular Genetic Analysis of Lysosomal Storage Disorder Genes in PDR01NS060113 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLARK, LORRAINE N · 2008 to 2011
$1.4MGenetic Analysis Of Non-Alzheimer DementiasZ01AG000951 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2002 to 2008
$647kCIHRIntramural NIH HHS Z01 AG000951Medical Research Council G0701075Medical Research Council MC_G1000735Medical Research Council MR/L010305/1Medical Research Council MR/L016397/1Medical Research Council MR/L022656/1NCATS NIH HHS UL1TR000040NIA NIH HHS AG000951-12NIA NIH HHS P50AG008702NINDS NIH HHS NS060113NINDS NIH HHS P50NS038370NINDS NIH HHS P50 NS072187NINDS NIH HHS R01 NS060113NINDS NIH HHS R01 NS078086Parkinson's UK G-0907Parkinson's UK K-1204Wellcome Trust 081864Wellcome Trust 089698Wellcome Trust 089701Wellcome Trust 089703Wellcome Trust 100140
Abstract
Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
Indexed as
alpha-SynucleinAlzheimer DiseaseApolipoproteins ECase-Control StudiesCohort StudiesFemaleGenetic Association StudiesGenetic LociHumansLewy Body DiseaseLysosomal Membrane ProteinsLysosomesMaleParkinson DiseaseReceptors, ScavengerRisk Factorsalpha-SynucleinApolipoproteins ELysosomal Membrane ProteinsReceptors, ScavengerSCARB2 protein, humanSNCA protein, human
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