Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease

Minerva M. Carrasquillo, Julia E. Crook, Otto Pedraza, Colleen S. Thomas, V. Shane Pankratz, Mariet Allen, Thuy Nguyen, Kimberly G. Malphrus, Li Ma, Gina D. Bisceglio, Rosebud O. Roberts, John A. Lucas, Glenn E. Smith, Robert J. Ivnik, Mary M. Machulda, Neill R. Graff-Radford, Ronald C. Petersen, Steven G. Younkin, Nilüfer Ertekin-Taner

Research output: Contribution to journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalNeurobiology of aging
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Alzheimer's disease
  • Association
  • Cognitive decline
  • Genetic risk
  • Memory
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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