Diffuse plaques contain C-terminal Aβ42 and not Aβ40: Evidence from cats and dogs

Brian J. Cummings, Takao Satou, Elizabeth Head, Norton W. Milgram, Greg M. Cole, Mary J. Savage, Marcia B. Podlisny, Dennis J. Selkoe, Robert Siman, Barry D. Greenberg, Carl W. Cotman

Research output: Contribution to journalArticlepeer-review

Abstract

Recent reports have suggested that β-amyloid (Aβ) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length Aβ42/3 fragments (i.e., Aβ forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both Aβ42/3 and Aβ40 (Aβ forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential Aβ deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of Aβ immunoreactive plaques, using antibodies to Aβ1-17, Aβ,17-24, Aβ1-28, Aβ40, and Aβ42. We report that plaques within the canine and feline brain are immunopositive for Aβ42 but not Aβ40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within Aβ1-17, Aβ17-24, and Aβ1-28. In all species examined, vascular deposits were immunopositive for both Aβ40 and Aβ42. In the human brain, diffuse plaques were preferentially Aβ42 immunopositive, while neuritic plaques and vascular deposits were both Aβ40 and Aβ42 immunopositive. However, not all neuritic plaques contain Aβ40 epitopes.

Original languageEnglish (US)
Pages (from-to)653-659
Number of pages7
JournalNeurobiology of Aging
Volume17
Issue number4
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid
  • Amyloid angiopathy
  • Animal models of aging
  • C-terminal epitope
  • Canine
  • Feline
  • Senile plaque development

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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