The proteolysis of beta-amyloid (Abeta) requires neprylisin, an enzyme that has been shown as reduced in Alzheimer's disease (AD). We investigated whether a decrease in neprilysin levels contributes to the accumulation of amyloid deposits not only in AD but also in the normal aging. We analyzed neprilysin mRNA and protein levels in cerebral cortex from 10 cognitively normal elderly subjects with amyloid plaques (NA), 10 cases of AD, and 10 control cases free of amyloid plaques. We found a significant decrease in neprilysin mRNA levels in both AD and NA compared to control cases. Thereby, the defect of neprilysin appears to correlate with Abeta deposition but not with degeneration and dementia.