AN INVIVO MODEL FOR THE NEURODEGENERATIVE EFFECTS OF BETA-AMYLOID AND PROTECTION BY SUBSTANCE-P

Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta-amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta-amyloid. Immunoblot analysis showed that beta-amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta-amyloid. Thus, beta-amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P.