PEN2 is not a genetic risk factor for Alzheimer's disease in a large family sample.

PEN2 is a reasonable Alzheimer's disease (AD) candidate gene because it is a necessary component of the gamma-secretase complex that generates beta-amyloid peptide. Moreover, its gene (PEN2) maps to a highly significant linkage region on chromosome 19q13. Four common polymorphisms in PEN2 were tested for genetic association with AD in a large and carefully ascertained AD family sample (789 subjects from 202 nuclear families) using single-locus and haplotype-based analyses. These results do not suggest PEN2 to be a major AD risk factor.