Declining expression of neprilysin in Alzheimer disease vasculature: Possible involvement in cerebral amyloid angiopathy

Molecular, genetic, and pharmacological studies have shown that neprilysin (also called NEP) catabolizes amyloid beta peptides (Abeta) in healthy conditions. However. in Alzheimer disease (AD), Abeta accumulates forming- senile plaques in brain parenchyma and amyloid deposition around blood vessels, In this study, we tested at cellular level the relationship between neprilysin and Abeta in human healthy and AD brain. Our results provided evidence for declining levels of neprilysin in AD brains as compared to healthy controls in parallel with increasing deposition of Abeta. In hippocampus of AD individuals we observed a significant clown-regulation of neprilysin expression in pyramidal neurons, consistent with the possibility that neprilysin controls the level of Abeta accumulation and plaque formation in this area. In the cortex and leptomeninges, neprilysin was expressed in the smooth muscle cells of blood vessels. In sections from AD patients we observed a clear inverse relationship between neprilysin and Abeta peptide levels in the vasculature, implicating neprilysin in cerebral amyloid angiopathy.