title: Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology.
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.
authors.affiliation: *Department of Biostatistics †National Alzheimer's Coordinating Center, University of Washington, Seattle, WA ‡Department of Biostatistics, University of Kentucky, Lexington, KY §Dept. of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY ∥Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MI.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.forename: Charles
authors.initials: C
authors.lastname: Mock
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.forename: Sarah
authors.initials: S
authors.lastname: Bertelsen
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Sally R
authors.initials: SR
authors.lastname: Ellingson
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D058070:Asymptomatic Diseases / Q000523:psychology; D030541:Databases, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters