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

Minerva M Carrasquillo, Juliana Crook, Otto D 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 Margaret Machulda, Neill R Graff Radford, Ronald Carl Petersen, Steven G Younkin, Nilufer Taner

Research output: Contribution to journalArticle

49 Citations (Scopus)

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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Alzheimer Disease
Genome-Wide Association Study
Cognitive Dysfunction

Keywords

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

ASJC Scopus subject areas

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

Cite this

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. / Carrasquillo, Minerva M; Crook, Juliana; Pedraza, Otto D; Thomas, Colleen S.; Pankratz, V. Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G.; Ma, Li; Bisceglio, Gina D.; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E.; Ivnik, Robert J.; Machulda, Mary Margaret; Graff Radford, Neill R; Petersen, Ronald Carl; Younkin, Steven G; Taner, Nilufer.

In: Neurobiology of Aging, Vol. 36, No. 1, 01.01.2015, p. 60-67.

Research output: Contribution to journalArticle

Carrasquillo, Minerva M ; Crook, Juliana ; Pedraza, Otto D ; Thomas, Colleen S. ; Pankratz, V. Shane ; Allen, Mariet ; Nguyen, Thuy ; Malphrus, Kimberly G. ; Ma, Li ; Bisceglio, Gina D. ; Roberts, Rosebud O ; Lucas, John A ; Smith, Glenn E. ; Ivnik, Robert J. ; Machulda, Mary Margaret ; Graff Radford, Neill R ; Petersen, Ronald Carl ; Younkin, Steven G ; Taner, Nilufer. / Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. In: Neurobiology of Aging. 2015 ; Vol. 36, No. 1. pp. 60-67.
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AU - Pankratz, V. Shane

AU - Allen, Mariet

AU - Nguyen, Thuy

AU - Malphrus, Kimberly G.

AU - Ma, Li

AU - Bisceglio, Gina D.

AU - Roberts, Rosebud O

AU - Lucas, John A

AU - Smith, Glenn E.

AU - Ivnik, Robert J.

AU - Machulda, Mary Margaret

AU - Graff Radford, Neill R

AU - Petersen, Ronald Carl

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