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Title | Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Monsell SE, Mock C, Fardo DW, Bertelsen S, Cairns NJ, Roe CM, Ellingson SR, Morris JC, Goate AM, Kukull WA |
Journal | Alzheimer Dis Assoc Disord |
Volume | 31 |
Issue | 3 |
Pagination | 232-238 |
Date Published | 2017 Jul-Sep |
ISSN | 1546-4156 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Asymptomatic Diseases, ATP-Binding Cassette Transporters, Databases, Genetic, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide |
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. |
DOI | 10.1097/WAD.0000000000000179 |
Alternate Journal | Alzheimer Dis Assoc Disord |
PubMed ID | 27849641 |
PubMed Central ID | PMC5432419 |
Grant List | P30 AG013854 / AG / NIA NIH HHS / United States P30 AG010124 / AG / NIA NIH HHS / United States P50 AG023501 / AG / NIA NIH HHS / United States K25 AG043546 / AG / NIA NIH HHS / United States RC2 AG036528 / AG / NIA NIH HHS / United States U01 AG032438 / AG / NIA NIH HHS / United States P50 AG005142 / AG / NIA NIH HHS / United States P50 AG005131 / AG / NIA NIH HHS / United States P30 AG010133 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States P50 AG016574 / AG / NIA NIH HHS / United States P50 AG005146 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States P30 AG035982 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States P01 AG003991 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P01 AG026276 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States S10 OD018522 / OD / NIH HHS / United States P30 AG012300 / AG / NIA NIH HHS / United States P50 AG016573 / AG / NIA NIH HHS / United States U24 AG041689 / AG / NIA NIH HHS / United States P50 AG016570 / AG / NIA NIH HHS / United States P50 AG005134 / AG / NIA NIH HHS / United States P30 AG008017 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States KL2 TR000116 / TR / NCATS NIH HHS / United States P50 AG025688 / AG / NIA NIH HHS / United States U01 AG049508 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 AG005138 / AG / NIA NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P30 AG019610 / AG / NIA NIH HHS / United States UL1 TR001998 / TR / NCATS NIH HHS / United States KL2 TR001996 / TR / NCATS NIH HHS / United States P30 AG028383 / AG / NIA NIH HHS / United States P50 AG033514 / AG / NIA NIH HHS / United States R01 AG035083 / AG / NIA NIH HHS / United States |