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Updated: Jun 24, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
The interaction of beta-amyloid protein with cellular membranes stimulates its own production
Imke Peters1, Urule Igbavboa, Tanja Schütt
1Department of Pharmacology, Goethe-University of Frankfurt am Main, Campus Riedberg, Biocenter Geb. N260, R.1.09, Max-von-Laue Str. 9, D-60438 Frankfurt, Germany.
Abstract:
Gradual changes in steady-state levels of beta amyloid peptides (Abeta) in brain are considered an initial step in the amyloid cascade hypothesis of Alzheimer's disease. Abeta is a product of the secretase cleavage of amyloid precursor protein (APP). There is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Cleavage of APP strongly depends on membrane properties. Since Abeta perturbs cell membrane fluidity, the cell membrane may be the location where the neurotoxic cascade of Abeta is initiated. Therefore, we tested effects of oligomeric Abeta on membrane fluidity of whole living cells, the impact of exogenous and cellular Abeta on the processing of APP and the role of GM-1 ganglioside. We present evidence that oligoAbeta((1-40)) stimulates the amyloidogenic processing of APP by reducing membrane fluidity and complexing with GM-1 ganglioside. This dynamic action of Abeta may start a vicious circle, where endogenous Abeta stimulates its own production. Based on our novel findings, we propose that oligoAbeta((1-40)) accelerates the proteolytic cleavage of APP by decreasing membrane fluidity.
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