title: An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P.
abstract: 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.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston 02114.
authors.forename: N W
authors.initials: NW
authors.lastname: Kowall
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
authors.forename: J
authors.initials: J
authors.lastname: Busciglio
authors.forename: L K
authors.initials: LK
authors.lastname: Duffy
authors.forename: B A
authors.initials: BA
authors.lastname: Yankner
mesh_terms: D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010455:Peptides / Q000138:chemical synthesis / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D013373:Substance P