Degeneration of vascular muscle cells in cerebral amyloid angiopathy of Alzheimer disease

Mitsuru Kawai, Rajesh N. Kalaria, Patrick Cras, Sandra L. Siedlak, Manuel E. Velasco, Earl R. Shelton, Hardy W. Chan, Barry D. Greenberg, George Perry

Research output: Contribution to journalArticlepeer-review

Abstract

In cerebral amyloid angiopathy, the amyloid-β (Aβ) deposits lie primarily in the tunica media suggesting that smooth muscle cells play an important role in Aβ deposition. To define this role, we conducted an immunocytochemical study of brain tissue from cases of Alzheimer disease with extensive cerebral amyloid angiopathy and cerebral hemorrhage. Antibodies specific to recombinant β protein precursor (βPP) and synthetic peptides homologous to various βPP sequences from residue 18 to 689 of βPP695 were used. Antibodies to actin, tropomyosin, α-actinin or desmin were used to label muscle cells. Antibodies to Aβ sequences intensely recognized the extracellular amyloid deposit. Antibodies raised against βPP sequences other than the Aβ domain recognized smooth muscle cells. βPP-immunoreactivity was reduced in regions of Aβ deposits, since no muscle cells were recognized by cytoskeletal markers or observed ultrastructurally. In order to assess why Aβ is deposited in the tunica media, we used biotin-labelled βPP to determine if βPP can be locally retained. We found βPP bound to the tunica media of vessels but not other brain elements. These findings suggest Aβ in blood vessels derives from degenerating βPP-containing smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)142-146
Number of pages5
JournalBrain research
Volume623
Issue number1
DOIs
StatePublished - Sep 24 1993
Externally publishedYes

Keywords

  • Amyloid β
  • Congophilic angiopathy
  • Smooth muscle
  • Vasculature
  • β Protein precursor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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