Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees.
Plasma Abeta42 (amyloid beta42 peptide) is invariably elevated in early-onset familial Alzheimer's disease (AD), and it is also increased in the first-degree relatives of patients with typical late-onset AD (LOAD). To detect LOAD loci that increase Abeta42, we used plasma Abeta42 as a surrogate trait and performed linkage analysis on extended AD pedigrees identified through a LOAD patient with extremely high plasma Abeta. Here, we report linkage to chromosome 10 with a maximal lod score of 3.93 at 81 centimorgans close to D10S1225. Remarkably, linkage to the same region was obtained independently in a genome-wide screen of LOAD sibling pairs. These results provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase Abeta.
Ertekin-Taner
N
N
Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.
Graff-Radford
N
N
Younkin
L H
LH
Eckman
C
C
Baker
M
M
Adamson
J
J
Ronald
J
J
Blangero
J
J
Hutton
M
M
Younkin
S G
SG
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D010641:Phenotype; D019655:Quantitative Trait, Heritable
D016229:Amyloid beta-Peptides; D005819:Genetic Markers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)