Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology

Sarah E. Monsell, Charles Mock, David W. Fardo, Sarah Bertelsen, Nigel J. Cairns, Catherine M. Roe, Sally R. Ellingson, John C. Morris, Alison M. Goate, Walter A. Kukull

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Objective: The objective was to determine whether symptomatic and asymptomatic persons with Alzheimer disease (AD) neuropathology have different allele counts for single-nucleotide polymorphisms that have been associated with clinical late-onset AD. Methods: Data came from the National Alzheimer's Coordinating Center Uniform Data Set and Neuropathology Data Set, and the Alzheimer's Disease Genetics Consortium (ADGC). Participants had low to high AD neuropathologic change. The 22 known/suspected genes associated with late-onset AD were considered. "Symptomatic" was defined as Clinical Dementia Rating global score >0. Results: Sixty-eight asymptomatic and 521 symptomatic participants met inclusion criteria. Single-nucleotide polymorphisms associated with ABCA7 [odds ratio (OR)=1.66; 95% confidence interval (CI), 1.03-2.85] and MAPT (OR=2.18; CI, 1.26-3.77) were associated with symptomatic status. In stratified analyses, loci containing CD2AP (OR=0.35; 95% CI, 0.16-0.74), ZCWPW1 (OR=2.98; 95% CI, 1.34-6.86), and MAPT (OR=3.73, 95% CI, 1.30-11.76) were associated with symptomatic status in APOE e4 carriers. Conclusions: These findings potentially explain some of the variation in whether a person with AD neuropathology expresses symptoms. Understanding why some people remain cognitively normal despite having AD neuropathology could identify pathways to disease heterogeneity and guide treatment trials.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalAlzheimer disease and associated disorders
Volume31
Issue number3
DOIs
StatePublished - 2017

Keywords

  • APOE
  • Alzheimer disease
  • Alzheimer disease genetics
  • genetic risk score
  • preclinical Alzheimer disease

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