No association between an intronic biallelic polymorphism of the FE65 geneand Alzheimer's disease

The cleavage of the amyloid precursor protein (APP) into amyloidogenic comp onents (AO) is a central event in the pathogenesis of Alzheimer's disease ( AD). FE65 is a protein that is involved in APP metabolism and may facilitat e the production of A beta. Recently, an intronic polymorphism of the gene encoding FE65 (FE65) was associated with altered risk for the development o f sporadic AD. In our sample of 102 AD patients and 351 non-demented contro ls we did not replicate the association between FE65 and AD. Moreover, we o bserved no risk-modifying interaction and no linkage disequilibrium between FE65 and the gene encoding the acid protease cathepsin D (catD), which - l ike FE65 - is involved in APP metabolism and is also located on chromosome 11p15. We conclude that, whereas FE65 is implicated in AD pathology, the ge ne encoding FE65 does not apper to confer a substantial risk for AD.