Association of neprilysin polymorphism with cerebral amyloid angiopathy.

Objectives: The risk of sporadic cerebral amyloid angiopathy (CAA) may be associated with genetic polymorphisms of molecules related to anabolism or catabolism of amyloid beta protein (Abeta). The authors investigated whether a polymorphism of the gene (NEP) coding for neprilysin, an enzyme catabolising Abeta, is associated with CAA. Methods: The study analysed the GT repeat polymorphism in the enhancer/promoter region of NEP and severity of CAA in 164 necropsied elderly Japanese subjects. Results: The subjects had NEP polymorphisms with 19 to 23 GT repeats and were classified into nine genotypes. CAA severity was significantly higher in the subjects with up to 40 repeats in total than those with more than 40 repeats (p=0.005). There was a significant correlation between the number of the shorter alleles (19 or 20 repeats) and CAA severity (p=0.024). In addition, there was no interaction between the NEP polymorphism and apolipoprotein E genotype. Conclusions: These results suggest the association between the NEP polymorphism and the risk of CAA. Further study using more samples from populations with different ethnic backgrounds is necessary.