期刊
NEUROBIOLOGY OF AGING
卷 36, 期 1, 页码 60-67出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.07.042
关键词
Alzheimer's disease; Memory; Mild cognitive impairment; Genetic risk; Association; Cognitive decline
资金
- National Institutes of Health: National Institute on Aging [R01 AG032990, R01 AG018023, AG025711, AG017216, AG003949]
- National Institutes of Health: National Institutes on Neurologic Diseases and Stroke [R01 NS080820]
- National Institutes of Health: Mayo Alzheimer's Disease Research Center [P50 AG0016574]
- National Institutes of Health: Mayo Alzheimer's Disease Patient Registry [U01 AG006576]
- Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program
- Palumbo Professorship in Alzheimer's Disease Research
- GHR Foundation
We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n >2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557- A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. (C) 2015 Elsevier Inc. All rights reserved.
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