Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide.

We recently demonstrated that amyloid beta peptide (Abeta) is catabolized primarily by a neutral endopeptidase, neprilysin, in the brain and that a neuropeptide, somatostatin (SST), regulates brain Abeta level via modulation of neprilysin activity. Because SST expression in the brain declines upon aging in various mammals including rodents, apes and humans, we hypothesize that the aging-dependent reduction of SST triggers accumulation of Abeta in the brain by suppressing neprilysin action. This hypothesis accounts for the fact that aging is the predominant risk factor for Sporadic Alzheimer's disease.