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

The cleavage of the amyloid precursor protein (APP) into amyloidogenic components (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 facilitate the production of A beta. Recently, an intronic polymorphism of the gene encoding FE65 (FE65) was associated with altered risk for the development of sporadic AD. In our sample of 102 AD patients and 351 non-demented controls we did not replicate the association between FE65 and AD. Moreover, we observed no risk-modifying interaction and no linkage disequilibrium between FE65 and the gene encoding the acid protease cathepsin D (catD), which - like FE65 - is involved in APP metabolism and is also located on chromosome 11p15. We conclude that, whereas FE65 is implicated in AD pathology, the gene encoding FE65 does not apper to confer a substantial risk for AD.