@article{bce335d94a6f4a2197a77ee95445b3ad,
title = "Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease",
abstract = "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.",
keywords = "Alzheimer's disease, Association, Cognitive decline, Genetic risk, Memory, Mild cognitive impairment",
author = "Carrasquillo, {Minerva M.} and Crook, {Julia E.} and Otto Pedraza and Thomas, {Colleen S.} and Pankratz, {V. Shane} and Mariet Allen and Thuy Nguyen and Malphrus, {Kimberly G.} and Li Ma and Bisceglio, {Gina D.} and Roberts, {Rosebud O.} and Lucas, {John A.} and Smith, {Glenn E.} and Ivnik, {Robert J.} and Machulda, {Mary M.} and Graff-Radford, {Neill R.} and Petersen, {Ronald C.} and Younkin, {Steven G.} and Nil{\"u}fer Ertekin-Taner",
note = "Funding Information: Support for this research was provided by the National Institutes of Health grants: National Institute on Aging ( R01 AG032990 to NET and R01 AG018023 to NRG-R and SGY); National Institutes on Neurologic Diseases and Stroke ( R01 NS080820 to NET), Mayo Alzheimer's Disease Research Center : ( P50 AG0016574 to RCP, DWD, NRG-R, SGY, and NET); Mayo Alzheimer's Disease Patient Registry : ( U01 AG006576 to RCP); National Institute on Aging ( AG025711 , AG017216 , AG003949 to DWD). This project was also generously supported by the Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program (to RCP, DWD, NRG-R, and SGY), and by the Palumbo Professorship in Alzheimer's Disease Research (to SGY). MMC and NET are supported partly by GHR Foundation grants. We thank Dr. Richard J. Caselli for useful discussion of the manuscript. We are grateful to our patients and their families for their participation, without whom these studies would not have been possible. Funding Information: R.C. Petersen, MD, PhD, has been a consultant to GE Healthcare and Elan Pharmaceuticals, has served on a data safety monitoring board in clinical trials sponsored by Pfizer Incorporated and Janssen Alzheimer Immunotherapy and gave a CME lecture at Novartis Incorporated. N. Graff-Radford, MD, has served as a consultant to Codman and received grant support from Elan Pharmaceutical Research, Pfizer Pharmaceuticals, Medivation, and Forrest. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jan,
day = "1",
doi = "10.1016/j.neurobiolaging.2014.07.042",
language = "English (US)",
volume = "36",
pages = "60--67",
journal = "Neurobiology of aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "1",
}