Genetic association of the presenilin-1 regulatory region with early-onsetAlzheimer's disease in a population-based sample

Genetic association has been reported between a di-allelic polymorphism in intron 8 of presenilin-1 (PSEN1) and Alzheimer's disease (AD) in some studi es but not in others. In a population-based series of 102 patients with ear ly onset AD and 118 community controls we examined whether polymorphisms in linkage disequilibrium with intron 8 of PSEN1 may explain the association. In addition to the intron 8 polymorphism (P = 0.05), a promoter polymorphi sm (P = 0.03) and the simple tandem repeat (STR) polymorphism D14S1028 loca ted upstream of PSEN1 (P = 0.04) were found to be marginally significantly associated to ED. When excluding PSEN1 mutation cases (n = 6), the intron 8 association was explained by linkage disequilibrium to the dominant PSEN1 mutations. In the non-mutation cases, the weak associations between the pol ymorphisms in the regulatory region remained. Our study suggests that a pol ymorphism/mutation in the promoter or regulatory region of PSEN1 rather tha n the polymorphism in intron 8 of PSEN1 is associated with early onset AD.