Amyloid-β aggregates induced by β-cholesteryl glucose-embedded liposomes

Area of Science:

• Neuroscience
• Biochemistry
• Materials Science

Background:

• Senile plaques, characteristic of Alzheimer's disease, are amyloid depositions primarily composed of aggregated amyloid-beta (Aβ) fibrils.
• Monitoring senile plaque formation on neuronal membranes under physiological conditions is crucial for understanding Alzheimer's disease.
• Amyloid fibril aggregation and associated toxicity are key factors in neurodegenerative amyloidopathies.

Purpose of the Study:

• To investigate the growth behavior of amyloid-beta (Aβ) fibrils in the presence of liposomes incorporating β-cholesteryl-D-glucose (β-CG).
• To elucidate the role of β-CG in inducing and modulating Aβ fibril aggregation on liposomal membranes.
• To explore the potential of β-CG-induced aggregation as a counterbalance to amyloid fibril toxicity.

Main Methods:

• Total internal reflection fluorescence microscopy
• Transmittance electron microscopy
• Spectroscopic methods

Main Results:

• β-CG on liposome membranes induced spontaneous formation of spherulitic Aβ fibrillar aggregates.
• β-CG clusters on liposomes promoted Aβ accumulation and subsequent growth of spherulitic aggregates.
• Compared to cholesterol-induced fibrils, β-CG promoted glucose-induced agglomeration of Aβ fibrils and liposomes, forming spherulitic aggregates.

Conclusions:

• β-CG incorporation into liposomes facilitates the formation of spherulitic Aβ aggregates.
• This glucose-induced agglomeration mechanism may serve as a counterbalance to Aβ fibril growth and toxicity.
• The findings offer potential therapeutic strategies for amyloidopathies by modulating Aβ aggregation.