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Genetic Comparison of Symptomatic and Asymptomatic Persons With... » Isaúde
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Alzheimer Disease and Associated Disorders
2017-07-01 05:00:00

Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology

Descrição: 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.

Seção: Original Articles
Volume: 0
Autor: Mayeda, Elizabeth R.; Glymour, M. Maria; Quesenberry, Charles P. Jr; Whitmer, Rachel A.

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