Linkage of plasma Aβ42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees

Plasma A beta 42 (amyloid beta 42 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 A beta 42, we used plasma A beta 42 as a surrogate trait and performed Linkage analysis on extended AD pedigrees identified through a LOAD patient with extremely high plasma A beta. 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 A beta.