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PMID: 1714596 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 16 ·1991-08-15 ·Pages 7247-51

Kowall NW, Beal MF, Busciglio J, Duffy LK, Yankner BA

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.

MeSH Terms
Amyloid beta-Peptides/chemical synthesis,toxicity Animals Cell Count Cerebral Cortex/drug effects,pathology Hippocampus/drug effects,pathology Male Nerve Degeneration/drug effects Neurons/drug effects,pathology Peptides/chemical synthesis,toxicity Rats Rats, Inbred Strains Substance P/pharmacology
Chemicals
Amyloid beta-Peptides Peptides Substance P
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kowall N W
Department of Neurology, Massachusetts General Hospital, Boston 02114.
Beal M F
Busciglio J
Duffy L K
Yankner B A
References (29)
29 references, click to expand
  1. Amyloid beta-protein deposition in tissues other than brain in Alzheimer's disease.
    Nature. 1989 Sep 21;341(6239):226-30 PMID: 2528696
  2. Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease.
    Science. 1989 Jul 28;245(4916):417-20 PMID: 2474201
  3. Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease.
    Proc Natl Acad Sci U S A. 1988 Aug;85(16):6202-6 PMID: 2970636
  4. Alz-50 antibody recognizes Alzheimer-related neuronal changes.
    Ann Neurol. 1988 Apr;23(4):371-9 PMID: 3382173
  5. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease.
    N Engl J Med. 1989 Jun 1;320(22):1446-52 PMID: 2566117
  6. Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals.
    Neurosci Lett. 1988 Nov 11;93(2-3):191-6 PMID: 3241644
  7. Substance P-like immunoreactivity is reduced in Alzheimer's disease cerebral cortex.
    Neurology. 1987 Jul;37(7):1205-9 PMID: 2439949
  8. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor.
    Nature. 1987 Feb 19-25;325(6106):733-6 PMID: 2881207
  9. Alzheimer-related neuronal protein A68: specificity and distribution.
    Ann Neurol. 1987 Oct;22(4):521-6 PMID: 3435070
  10. Amyloid plaque core protein in Alzheimer disease and Down syndrome.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245-9 PMID: 3159021
  11. Peptides and the blood-brain barrier: lipophilicity as a predictor of permeability.
    Brain Res Bull. 1985 Sep;15(3):287-92 PMID: 2413968
  12. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.
    EMBO J. 1985 Nov;4(11):2757-63 PMID: 4065091
  13. Senile plaque amyloid, paired helical filaments, and cerebrovascular amyloid in Alzheimer's disease are all deposits of the same protein.
    Lancet. 1985 Feb 2;1(8423):278 PMID: 2857343
  14. A neuronal antigen in the brains of Alzheimer patients.
    Science. 1986 May 2;232(4750):648-50 PMID: 3083509
  15. Isolation of low-molecular-weight proteins from amyloid plaque fibers in Alzheimer's disease.
    J Neurochem. 1986 Jun;46(6):1820-34 PMID: 3517233
  16. Down patients: extracellular preamyloid deposits precede neuritic degeneration and senile plaques.
    Neurosci Lett. 1989 Feb 13;97(1-2):232-8 PMID: 2521927
  17. Amyloid beta protein enhances the survival of hippocampal neurons in vitro.
    Science. 1989 Mar 17;243(4897):1488-90 PMID: 2928783
  18. The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease.
    Acta Neuropathol. 1990;80(3):318-27 PMID: 1698007
  19. Golgi-like demonstration of "dark" neurons with an argyrophil III method for experimental neuropathology.
    Acta Neuropathol. 1990;79(6):620-8 PMID: 1694382
  20. Substance P immunoreactivity in Alzheimer disease: a study in cases presenting symmetric or asymmetric cortical atrophy.
    Alzheimer Dis Assoc Disord. 1990;4(1):24-34 PMID: 1690554
  21. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein.
    Biochem Biophys Res Commun. 1984 May 16;120(3):885-90 PMID: 6375662
  22. Cortical substance P-like immunoreactivity in cases of Alzheimer's disease and senile dementia of the Alzheimer type.
    J Neurochem. 1982 Jun;38(6):1781-4 PMID: 6176686
  23. Nerve growth factor potentiates the neurotoxicity of beta amyloid.
    Proc Natl Acad Sci U S A. 1990 Nov;87(22):9020-3 PMID: 2174172
  24. Substance P-like immunoreactive neurons are depleted in Alzheimer's disease cerebral cortex.
    Neuroscience. 1991;41(1):41-60 PMID: 1711654
  25. A68: a major subunit of paired helical filaments and derivatized forms of normal Tau.
    Science. 1991 Feb 8;251(4994):675-8 PMID: 1899488
  26. Alz-50 recognizes a phosphorylated epitope of tau protein.
    J Neurosci. 1990 Oct;10(10):3295-304 PMID: 1698946
  27. Neurochemical characterization of excitotoxin lesions in the cerebral cortex.
    J Neurosci. 1991 Jan;11(1):147-58 PMID: 1670782
  28. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides.
    Science. 1990 Oct 12;250(4978):279-82 PMID: 2218531
  29. Does amyloid precede paired helical filaments in the senile plaque? A study of 15 cases with graded intellectual status in aging and Alzheimer disease.
    Neurosci Lett. 1988 Sep 12;91(3):354-9 PMID: 2460803
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.16.7247
Published
1991-08-15
Pages
7247-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52271
Subset
IM
Grants
NIA NIH HHS · AG09229 · United States
NINDS NIH HHS · NS01240 · United States
NINDS NIH HHS · NS10828 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.16.7247 PMC Full Text View journal details
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