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Updated: Aug 19, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
GM1 ganglioside-mediated accumulation of amyloid beta-protein on cell membranes
Masaki Wakabayashi1, Takuma Okada, Yasunori Kozutsumi
1Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
The conversion of soluble, nontoxic amyloid beta-protein (Abeta) to aggregated, toxic Abeta is the key step in the development of Alzheimer's disease. Liposomal studies proposed that Abeta specifically recognizes a cholesterol-dependent cluster of monosialoganglioside GM1 and a conformationally altered form of Abeta promotes the aggregation of the protein. In this study, the accumulation of Abeta on living cells was investigated for the first time. The interaction of fluorescein-labeled Abeta (FL-Abeta) with rat pheochromocytoma PC12 cells was visualized using confocal laser microscopy. FL-Abeta was found to colocalize with GM1-rich domains on cell membranes and to accumulate in a concentration- and time-dependent manner, leading to cytotoxicity. Cholesterol depletion significantly reduced Abeta accumulation. These observations corroborate the GM1-mediated Abeta accumulation model.
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