Association study of the GAB2 gene with the risk of developing Alzheimer's disease.

The first genome-wide association in Alzheimer's disease (AD) suggested that the GAB2 gene rs2373115 polymorphism may be a strong risk factor in APOE varepsilon4-carriers. We failed to detect an association of rs2373115 with the risk of developing AD in three populations (totalling 1406 controls and 1749 AD cases) whatever the APOE status, even if we observed a slight tendency for an increase of the GG genotype (OR (GG versus GT+TT)=1.3, 95% CI 1.0-1.6, p=0.09) and the G allele frequency (OR=1.3, 95%CI 1.0-1.6, p=0.05) in varepsilon4-carriers. In addition, the rs2373115 did not modulate the extent of tau phosphorylation in the brain of 89 AD cases. The GAB2 gene is at best a minor genetic determinant of AD.