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Amyloid formation in Alzheimer’s may be modulated by vesicles formed by cholesterol derivatives

Anomalous protein aggregation has been pinpointed as a prime cause of a number of serious neurodegenerative diseases that include Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob. In the case of Alzheimer’s, protein aggregation starts with cleavage of an amyloid precursor protein (APP) by a secretase to form amyloid-β (Aβ), a family of peptides that form toxic fibrillar plaques, leading to progressive neuron degeneration. This insight has hastened the search for methods to prevent plaque formation. The cholesterol-rich membrane microdomains that promote secretase activity appear to be involved. Added to that, free cholesterol in the cytoplasm can promote the aggregation of Aβ peptides into fibrils, and cholesterol can interact directly with APP and Aβ amyloid fibrils. With this in mind, Elbassal and colleagues at Florida Atlantic University, USA, investigated how cholesterol and its derivatives could affect the formation of fibrils. They showed that the structural properties of the cholesterol-derivative vesicles, including surface charge and vesicle size, are critical in regulating their effect on Aβ40 aggregation kinetics.

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