Variable expression of presenilin 1 is not a major determinant of risk forlate-onset Alzheimer's Disease

We have previously reported a significant association between early-onset A lzheimer's disease (EOAD) and an allele in the promoter of presenilin 1 (PS EN1) significantly decreasing PSEN1 expression in vitro. For late-onset Alz heimer's disease (LOAD), numerous studies have reported inconsistent associ ations with a PSEN1 intronic polymorphism. We therefore hypothesized that l inkage disequilibrium between the intronic PSEN1 polymorphism and the funct ional promoter polymorphism might explain the conflicting reports in LOAD. We analysed both variations in 356 LOAD patients and 230 controls in a popu lation-based case-control study. In addition, we re-analysed all published literature on the PSEN1 intronic polymorphism in a metaanalysis. No signifi cant association was found with the PSEN1 intronic or promoter polymorphism in our case-control sample. In the metaanalysis no major differences betwe en patients and controls were found for the PSEN1 intronic variation. Toget her, our results do not support a major role for variable expression of PSE N1 in LOAD.