Amyloid-β-protein isoforms in brain of subjects with PS1-linked, βAPP-linked and sporadic Alzheimer disease

Akira Tamaoka, Paul E. Fraser, Kazuhiro Ishii, Naruhiko Sahara, Kazuharu Ozawa, Masaki Ikeda, Ann M. Saunders, Yasuko Komatsuzaki, Robin Sherrington, Georges Levesque, Gang Yu, Ekaterina Rogaeva, Shin'Ichi Shoji, Linda E. Nee, Daniel A. Pollen, Lydia Hendriks, Jean J. Martin, Christine Van Broeckhoven, Allen D. Roses, Lindsay A. FarrerPeter H. St. George-Hyslop, Hiroshi Mori

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

To determine whether similar abnormalities of various soluble full-length and N-terminal truncated Aβ peptides occur in postmortem cerebral cortex of affected PS1 mutation carriers, we examined the amounts of two amyloid species ending at residue 40 or at residues 42(43) using sandwich ELISA systems. Our results indicate that PS1 mutations effect a dramatic accumulation in brain of the highly insoluble potentially neurotoxic long-tailed isoforms of the Aβ peptide such as Aβ1-42(43) and Aβx-42(43). This enhancing effect of PS1 mutation on Aβx-42(43) deposition was highly similar to that of a βAPP mutation (Val717Ile) but the effects on Aβx-40 production were significantly different between these two causal genes. In contrast to previous studies of soluble Aβ in plasma and in supernatants from cultured fibroblasts of subjects with PS1 mutations, our studies also show that there is an increase in insoluble Aβx-40 peptides in brain of subjects with PS1 mutations.

Original languageEnglish (US)
Pages (from-to)178-185
Number of pages8
JournalMolecular Brain Research
Volume56
Issue number1-2
DOIs
StatePublished - May 1 1998

Keywords

  • APP717
  • Alzheimer's disease
  • Amyloid deposition
  • Insoluble
  • Presenilin-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Tamaoka, A., Fraser, P. E., Ishii, K., Sahara, N., Ozawa, K., Ikeda, M., Saunders, A. M., Komatsuzaki, Y., Sherrington, R., Levesque, G., Yu, G., Rogaeva, E., Shoji, SI., Nee, L. E., Pollen, D. A., Hendriks, L., Martin, J. J., Van Broeckhoven, C., Roses, A. D., ... Mori, H. (1998). Amyloid-β-protein isoforms in brain of subjects with PS1-linked, βAPP-linked and sporadic Alzheimer disease. Molecular Brain Research, 56(1-2), 178-185. https://doi.org/10.1016/S0169-328X(98)00044-8