Abundance of the longer Aβ42 in neocortical and cerebrovascular amyloid β deposits in Swedish familial Alzheimer's disease and Down's syndrome

R. N. Kalaria, D. L. Cohen, B. D. Greenberg, M. J. Savage, N. E. Bogdanovic, B. Winblad, L. Lannfelt, A. Adem

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have demonstrated the deposition of amyloid β (Aβ) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to Aβ peptides, we examined the immunocytochemical distribution of Aβ40 and Aβ42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid β precursor protein (AβPP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal Aβ deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. Aβ42 was evident in almost all parenchymal deposits as well as many vascular deposits. Although Aβ40 was present in meningeal and intraparenchymal vessels, deposits containing this shorter peptide reactivity were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable abundance of Aβ42 in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published AβPP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble Aβ production and Aβ42 species to be predominant, it would appear that the double AβPP mutations in Swedish FAD largely result in the deposition of the longer Aβ42 in vivo.

Original languageEnglish (US)
Pages (from-to)1377-1381
Number of pages5
JournalNeuroreport
Volume7
Issue number8
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Amyloid β peptide
  • Carboxyl-terminal
  • Cerebral amyloid angiopathy
  • Cerebrovascular
  • Familial Alzheimer's disease
  • Neocortex

ASJC Scopus subject areas

  • Neuroscience(all)

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