Amyloid β protein (Aβ) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at Aβ40 or Aβ42(43)

S. A. Gravina, L. Ho, C. B. Eckman, K. E. Long, L. Otvos, L. H. Younkin, N. Suzuki, S. G. Younkin

Research output: Contribution to journalArticle

524 Scopus citations

Abstract

Biochemical and immunocytochemical analyses were performed to evaluate the composition of the amyloid β protein (Aβ) deposited in the brains of patients with Alzheimer's disease (AD). To quantitate all Aβs present, cerebral cortex was homogenized in 70% formic acid, and the supernatant was analyzed by sandwich enzyme-linked immunoabsorbent assays specific for various forms of Aβ. In 9 of 27 AD brains examined, there was minimal congophilic angiopathy and virtually all (96%) ended at Aβ42(43). The other 18 AD brains contained increasing amounts of Aβ ending at Aβ40. From this set, 6 brains with substantial congophilic angiopathy were separately analyzed. In these brains, the amount of Aβ ending at Aβ42(43) was much the same as in brains with minimal congophilic angiopathy, but a large amount of Aβ ending at Aβ40 (76% of total Aβ) was also present. Immunocytochemical analysis with monoclonal antibodies selective for Aβs ending at Aβ42(43) or Aβ40 confirmed that, in brains with minimal congophilic angiopathy, virtually all Aβ is Aβ ending at Aβ42(43) and showed that this Aβ is deposited in senile plaques of all types. In the remaining AD brains, Aβ42(43) was deposited in a similar fashion in plaques, but, in addition, widely varying amounts of Aβ ending at Aβ40 were deposited, primarily in blood vessel walls, where some Aβ ending at Aβ42(43) was also present. These observations indicate that Aβs ending at Aβ42(43), which are a minor component of the Aβ in human cerebrospinal fluid and plasma, are critically important in AD where they deposit selectively in plaques of all kinds.

Original languageEnglish (US)
Pages (from-to)7013-7016
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number13
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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