Dissociation of β-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates β-amyloid-42 assembly

Ayumi Takamura, Takeshi Kawarabayashi, Tatsuki Yokoseki, Masao Shibata, Maho Morishima-Kawashima, Yuko Saito, Shigeo Murayama, Yasuo Ihara, Koji Abe, Mikio Shoji, Makoto Michikawa, Etsuro Matsubara

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Monoclonal 2C3 specific to β-amyloid (Aβ) oligomers (AβOs) enabled us to test our hypothesis that the alteration of lipoprotein-Aβ interaction in the central nervous system (CNS) initiates and/or accelerates the cascade favoring Aβ assembly. Immunoprecipitation of frontal cortex employing 2C3 unequivocally detected soluble 4-, 8-, and 12-mers in Alzheimer's disease (AD) brains. Immunoblot analysis of the entorhinal cortex employing 2C3 revealed that the accumulation of soluble 12-mers precedes the appearance of neuronal loss or cognitive impairment and is enhanced as the Braak neurofibrially tangle (NFT) stages progress. The dissociation of soluble Aβ from lipoprotein particles occurs in cerebrospinal fluid (CSF), and the presence of lipoprotein-free oligomeric 2C3 conformers (4- to 35-mers) was evident, which mimic CNS environments. Such CNS environments may strongly affect conformation of soluble Aβ peptides, resulting in the conversion of soluble Aβ42 monomers into soluble Aβ42 assembly. The findings suggest that functionally declined lipoproteins may accelerate the generation of metabolic conditions leading to higher levels of soluble Aβ42 assembly in the CNS.

Original languageEnglish
Pages (from-to)815-821
Number of pages7
JournalJournal of Neuroscience Research
Volume89
Issue number6
DOIs
Publication statusPublished - Jun 1 2011

Keywords

  • Alzheimer's disease
  • Lipoprotein
  • Monomer
  • Oligomer

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Takamura, A., Kawarabayashi, T., Yokoseki, T., Shibata, M., Morishima-Kawashima, M., Saito, Y., Murayama, S., Ihara, Y., Abe, K., Shoji, M., Michikawa, M., & Matsubara, E. (2011). Dissociation of β-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates β-amyloid-42 assembly. Journal of Neuroscience Research, 89(6), 815-821. https://doi.org/10.1002/jnr.22615