Cited by 222Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsGenetic Associations and Epidemiology

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Genetic Variation and Neuroimaging Measures in Alzheimer Disease

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Biffi, Alessandro·2010·Archives of Neurology

DOI 10.1001/archneurol.2010.108PMC PMC2956757

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Abstract

OBJECTIVE: To investigate whether genome-wide association study (GWAS)-validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status. DESIGN: Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative. SETTING: Multicenter GWAS. Patients A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. MAIN OUTCOME MEASURES: We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. RESULTS: Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate-corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score-based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). CONCLUSIONS: Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.

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Authors: Biffi, A.
Affiliations: Massachusetts General Hospital (US)
Corresponding author: Biffi, Alessandro
ORCID: Biffi, Alessandro
Venue: Archives of Neurology
Publisher: American Medical Association (AMA)
Published: 2010-06-01
Volume: 67
Issue: 6
Pages: 677
ISSN: 0003-9942 (ISSN-L)
DOI: 10.1001/archneurol.2010.108
PMC: PMC2956757
OpenAlex: W2105172870
Cited by: 222
References: 36
Citations by year: 2026: 2 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 12 · 2021: 9 · 2020: 14 · 2019: 17 · 2018: 14 · 2017: 9 · 2016: 28 · 2015: 14 · 2014: 19 · 2013: 26 · 2012: 14
FWCI: 14.83
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Archives of Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Foundation for the National Institutes of Health (U01AG024904, AG024904)
Howard Hughes Medical Institute
Ellison Medical Foundation
Alzheimer's Association (AG05681, U01 AG024904)
American Heart Association
Bristol-Myers Squibb (U01 AG024904, AG024904)
Eli Lilly and Company (U01 AG024904, AG024904)
Pfizer (AG024904, U01 AG024904)
GlaxoSmithKline (P01AG03991)
Northern California Institute for Research and Education (U01 AG024904)
Elan (U01 AG024904)
Eisai (U01 AG024904, AG024904)
National Institutes of Health (5u01ag024904-10, 6u54rr020278-06, BIRN002, U01-AG024904, AG05681, RR14075, AG024904, NS042861)
University of California, Los Angeles
University of California, San Diego
National Institute on Aging (U01-AG-024904, AG021910, P30AG010129, R01AG021910, R01AG026484, AG 024904, K01AG030514, AG 05681, P 50 AG05681, P50AG005681, P01 AG0 3991, P01AG003991, AG02238, U19AG010483, U24AG021886)
National Institute on Drug Abuse (R21DA026104)
National Institute of Neurological Disorders and Stroke (R01NS042861, R01NS059727, R01NS052585)
National Institute of Biomedical Imaging and Bioengineering (R01EB001550, R01EB006758, U01 AG024904, AG024904)
National Center for Research Resources (U54-RR020278, P41-RR-14075, RR 14075, U24RR021382, R01 RR1659401A1, P41RR014075, BIRN002, R01RR016594, U01 AG024904)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: Alzheimer's disease, genetic loci, genome-wide association study, hippocampal volume, amygdala volume, white matter lesions, cortical thickness, apolipoprotein E, complement receptor 1, PICALM, BIN1, CNTN5, mild cognitive impairment, Alzheimer's Disease Neuroimaging Initiative
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Canada, Cognition Disorders, Female, Genotype, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Nuclear Proteins, Risk Factors, United States, Reproducibility of Results, Cell Adhesion Molecules, Neuronal, Logistic Models, Odds Ratio, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study

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