GAB2 Alleles Modify Alzheimer’s Risk in APOE ε4 Carriers

Eric M Reiman; Jennifer A Webster; Amanda J Myers; John Hardy; Travis Dunckley; Victoria L Zismann; Keta D Joshipura; John V Pearson; Diane Hu-Lince; Matthew J Huentelman; David W Craig; Keith D Coon; Winnie S Liang; RiLee H Herbert; Thomas Beach; Kristen C Rohrer; Alice S Zhao; Doris Leung; Leslie Bryden; Lauren Marlowe; Mona Kaleem; Diego Mastroeni; Andrew Grover; Christopher B Heward; Rivka Ravid; Joseph Rogers; Michael L Hutton; Stacey Melquist; Ron C Petersen; Gene E Alexander; Richard J Caselli; Walter Kukull; Andreas Papassotiropoulos; Dietrich A Stephan

doi:10.1016/j.neuron.2007.05.022

Back

GAB2 Alleles Modify Alzheimer’s Risk in APOE ε4 Carriers

Journal article

Peer reviewed

GAB2 Alleles Modify Alzheimer’s Risk in APOE ε4 Carriers

Eric M Reiman, Jennifer A Webster, Amanda J Myers, John Hardy, Travis Dunckley, Victoria L Zismann, Keta D Joshipura, John V Pearson, Diane Hu-Lince, Matthew J Huentelman, …

Neuron (Cambridge, Mass.), Vol.54(5), pp.713-720

2007-06-07

DOI: https://doi.org/10.1016/j.neuron.2007.05.022

PMID: 17553421

Abstract

The apolipoprotein E ( APOE ) ε4 allele is the best established genetic risk factor for late-onset Alzheimer’s disease (LOAD). We conducted genome-wide surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and confirm other LOAD susceptibility genes. In ε4 carriers from neuropathologically verified discovery, neuropathologically verified replication, and clinically characterized replication cohorts of 1411 cases and controls, LOAD was associated with six SNPs from the GRB -associated binding protein 2 ( GAB2 ) gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p = 9 × 10 −11 ) was associated with an odds ratio of 4.06 (confidence interval 2.81–14.69), which interacts with APOE ε4 to further modify risk. GAB2 was overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference with GAB2 gene expression increased tau phosphorylation. Our findings suggest that GAB2 modifies LOAD risk in APOE ε4 carriers and influences Alzheimer’s neuropathology.

Metrics

12 Record Views

381 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.57 Alzheimer's Disease
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: GAB2 Alleles Modify Alzheimer’s Risk in APOE ε4 Carriers
Creators: Eric M Reiman - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Jennifer A Webster - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Amanda J Myers - Department of Psychiatry and Behavioral Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
John Hardy - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Travis Dunckley - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Victoria L Zismann - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Keta D Joshipura - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
John V Pearson - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Diane Hu-Lince - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Matthew J Huentelman - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
David W Craig - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Keith D Coon - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Winnie S Liang - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
RiLee H Herbert - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Thomas Beach - Sun Health Research Institute, Sun City, AZ 85351, USA
Kristen C Rohrer - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Alice S Zhao - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Doris Leung - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Leslie Bryden - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Lauren Marlowe - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Mona Kaleem - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
Diego Mastroeni - Sun Health Research Institute, Sun City, AZ 85351, USA
Andrew Grover - Sun Health Research Institute, Sun City, AZ 85351, USA
Christopher B Heward - Kronos Science Laboratory, Phoenix, AZ 85016, USA
Rivka Ravid - Netherlands Institute for Neurosciences, Dutch Royal Academy of Arts and Sciences, Meibergdreef 47 AB Amsterdam, The Netherlands
Joseph Rogers - Sun Health Research Institute, Sun City, AZ 85351, USA
Michael L Hutton - Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
Stacey Melquist - Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
Ron C Petersen - Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Gene E Alexander - Department of Psychology, Arizona State University, Tempe, AZ 85281, USA
Richard J Caselli - Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA
Walter Kukull - National Alzheimer’s Coordinating Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA
Andreas Papassotiropoulos - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Dietrich A Stephan - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Publication Details: Neuron (Cambridge, Mass.), Vol.54(5), pp.713-720
Academic Unit: Miller School of Medicine; Cell Biology Research
Language: English
Resource Type: Journal article
PMID: 17553421
Record Identifier: 991031561896302976