The amyloid precursor protein locus and very-late-onset Alzheimer disease.
Although mutations in the amyloid-beta precursor protein (APP) gene are known to confer high risk of Alzheimer disease (AD) to a small percentage of families in which it has early onset, convincing evidence of a major role for the APP locus in late-onset AD has not been forthcoming. In this report, we have used a covariate-based affected-sib-pair linkage method to analyze the chromosome 21 clinical and genetic data obtained on affected sibships by the National Institute of Mental Health Alzheimer Disease Genetics Initiative. The baseline model (without covariates) gave a LOD score of 0.02, which increases to 1.43 when covariates representing the additive effects of E2 and E4 are added. Larger increases in LOD scores were found when age at last examination/death (LOD score 5.54; P=.000002) or age at onset plus disease duration (LOD score 5.63; P=.000006) were included in the linkage model. We conclude that the APP locus may predispose to AD in the very elderly.
Olson
J M
JM
Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109, USA. olson@darwin.cwru.edu
Goddard
K A
KA
Dudek
D M
DM
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009679:Nuclear Family
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E