@article {Monsell:2017:0893-0341:232,
title = "Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology",
journal = "Alzheimer Disease & Associated Disorders",
parent_itemid = "infobike://wk/wad",
publishercode ="wk",
year = "2017",
volume = "31",
number = "3",
publication date ="2017-07-01T00:00:00",
pages = "232-238",
itemtype = "ARTICLE",
issn = "0893-0341",
eissn = "1546-4156",
url = "https://www.ingentaconnect.com/content/wk/wad/2017/00000031/00000003/art00008",
doi = "doi:10.1097/WAD.0000000000000179",
keyword = "APOE, genetic risk score, Alzheimer disease genetics, Alzheimer disease, preclinical Alzheimer disease",
author = "Monsell, Sarah E. and Mock, Charles and Fardo, David W. and Bertelsen, Sarah and Cairns, Nigel J. and Roe, Catherine M. and Ellingson, Sally R. and Morris, John C. and Goate, Alison M. and Kukull, Walter A.",
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 Alzheimers Coordinating Center Uniform Data Set and Neuropathology Data Set, and the Alzheimers 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.",
}