A novel action of Alzheimer's amyloid β-protein (Aβ): Oligomeric Aβ promotes lipid release

Makoto Michikawa, Jian Sheng Gong, Qi Wen Fan, Naoya Sawamura, Katsuhiko Yanagisawa

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Interactions between amyloid β-protein (Aβ) and lipids have been suggested to play important roles in the pathogenesis of Alzheimer's disease. However, the molecular mechanism underlying these interactions has not been fully understood. We examined the effect of Aβ on lipid metabolism in cultured neurons and astrocytes and found that oligomeric Aβ, but not monomeric or fibrillar Aβ, promoted lipid release from both types of cells in a dose- and time-dependent manner. The main components of lipids released after the addition of Aβ were cholesterol, phospholipids, and monosialoganglioside (GM1). Density-gradient and electron microscopic analyses of the conditioned media demonstrated that these Aβ and lipids formed particles and were recovered from the fractions at densities of ∼1.08-1.18 g/ml, which were similar to those of high-density lipoprotein (HDL) generated by apolipoproteins. The lipid release mediated by Aβ was abolished by concomitant treatment with Congo red and the PKC inhibitor, H7, whereas it was not inhibited with N-acetyl-L-cysteine. These Aβ-lipid particles were not internalized into neurons, whereas HDL-like particles produced by apolipoprotein E were internalized. Our findings indicate that oligomeric Aβ promotes lipid release from neuronal membrane, which may lead to the disruption of neuronal lipid homeostasis and the loss of neuronal function.

Original languageEnglish
Pages (from-to)7226-7235
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number18
DOIs
Publication statusPublished - 2001 Sep 15

Keywords

  • Alzheimer's disease
  • Amyloid β-protein
  • Cholesterol release
  • Cultured neurons
  • High-density lipoprotein
  • Phospholipid

ASJC Scopus subject areas

  • Neuroscience(all)

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