Journal
NEUROIMAGE
Volume 51, Issue 2, Pages 542-554Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2010.02.068
Keywords
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Funding
- ADNI
- NIH [U01 AG024904, U54 RR021813]
- National Institute of Aging, the National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- Foundation for the National Institutes of Health
- Pfizer Inc.
- Wyeth Research
- Bristol-Myers Squibb
- Eli Lilly and Company
- GlaxoSmithKline
- Merck Co. Inc.
- AstraZeneca AB
- Novartis Pharmaceuticals Corporation
- Alzheimer's Association
- Eisai Global Clinical Development
- Elan Corporation plc
- Forest Laboratories
- Institute for the Study of Aging (ISOA)
- U.S. Food and Drug Administration
- National Center for Research Resources (NCRR) [P41 RR013642, M01 RR000865]
- NIBIB [R01 EB007813, R01 EB008281, R01 EB008432]
- NICHHD [R01 HD050735]
- NIA [R01 AG020098]
- NIH/NIDA [1-T90-DA022768:02]
- ARCS foundation
- NIMH [1F31MH087061]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD050735] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR021813, P41RR013642, M01RR000865] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K25HL080079] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB008281, R01EB008432, R01EB007813] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [F31MH087061] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS059873] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG020098, U24AG021886, U01AG024904, U19AG010483] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [T90DA022768] Funding Source: NIH RePORTER
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In a genome-wide association study of structural brain degeneration, we mapped the 3D profile of temporal lobe volume differences in 742 brain MRI scans of Alzheimer's disease patients, mildly impaired, and healthy elderly subjects. After searching 546,314 genomic markers, 2 single nucleotide polymorphisms (SNPs) were associated with bilateral temporal lobe volume (P<5 x 10(-7)). One SNP, rs10845840, is located in the GRIN2B gene which encodes the N-methyl-D-aspartate (NMDA) glutamate receptor NR2B subunit. This protein involved in learning and memory, and excitotoxic cell death - has age-dependent prevalence in the synapse and is already a therapeutic target in Alzheimer's disease. Risk alleles for lower temporal lobe volume at this SNP were significantly over-represented in AD and MCI subjects vs. controls (odds ratio = 1.273; P = 0.039) and were associated with mini-mental state exam scores (MMSE; t = 2.114; P=0.035) demonstrating a negative effect on global cognitive function. Voxelwise maps of genetic association of this SNP with regional brain volumes, revealed intense temporal lobe effects (FDR correction at q=0.05: critical P=0.0257). This study uses large-scale brain mapping for gene discovery with implications for Alzheimer's disease. (C) 2010 Elsevier Inc. All rights reserved.
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