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

130 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
Publication statusPublished - 2001 Sep 15
Externally publishedYes

Fingerprint

Serum Amyloid A Protein
Lipids
HDL Lipoproteins
Neurons
Congo Red
Apolipoproteins
Acetylcysteine
Apolipoproteins E
Conditioned Culture Medium
Lipid Metabolism
Astrocytes
Phospholipids
Alzheimer Disease
Homeostasis
Cholesterol
Electrons
Membranes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Michikawa, M., Gong, J. S., Fan, Q. W., Sawamura, N., & Yanagisawa, K. (2001). A novel action of Alzheimer's amyloid β-protein (Aβ): Oligomeric Aβ promotes lipid release. Journal of Neuroscience, 21(18), 7226-7235.

A novel action of Alzheimer's amyloid β-protein (Aβ) : Oligomeric Aβ promotes lipid release. / Michikawa, Makoto; Gong, Jian Sheng; Fan, Qi Wen; Sawamura, Naoya; Yanagisawa, Katsuhiko.

In: Journal of Neuroscience, Vol. 21, No. 18, 15.09.2001, p. 7226-7235.

Research output: Contribution to journalArticle

Michikawa, M, Gong, JS, Fan, QW, Sawamura, N & Yanagisawa, K 2001, 'A novel action of Alzheimer's amyloid β-protein (Aβ): Oligomeric Aβ promotes lipid release', Journal of Neuroscience, vol. 21, no. 18, pp. 7226-7235.
Michikawa, Makoto ; Gong, Jian Sheng ; Fan, Qi Wen ; Sawamura, Naoya ; Yanagisawa, Katsuhiko. / A novel action of Alzheimer's amyloid β-protein (Aβ) : Oligomeric Aβ promotes lipid release. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 18. pp. 7226-7235.
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