The interplay between lipid and Aβ amyloid homeostasis in Alzheimer’s Disease: risk factors and therapeutic opportunities

• Published in: Chemistry and physics of lipids 2021-05, Vol.236, p.105072, Article 105072
• Main Authors: García-Viñuales, Sara, Sciacca, Michele F.M., Lanza, Valeria, Santoro, Anna Maria, Grasso, Giulia, Tundo, Grazia R., Sbardella, Diego, Coletta, Massimiliano, Grasso, Giuseppe, La Rosa, Carmelo, Milardi, Danilo
• Format: Article
• Language: English
• Subjects: amyloid aggregation; lipid bilayer; membrane damage; proteasome; small molecules
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2021.105072

[Display omitted] •Besides familial inheritance, comorbidity with other diseases and a sedentary lifestyle are risk factors for AD development.•Alzheimer’s Diseases (AD) is often associated to dyslipidemia.•Accumulation of amyloid deposits of Aβ peptide in the AD brain is related to abnormal lipid metabolism.•Lipids interfere with amyloid clearance by affecting proteasome and autophagy activities Alzheimer’s Diseases (AD) is characterized by the accumulation of amyloid deposits of Aβ peptide in the brain. Besides genetic background, the presence of other diseases and an unhealthy lifestyle are known risk factors for AD development. Albeit accumulating clinical evidence suggests that an impaired lipid metabolism is related to Aβ deposition, mechanistic insights on the link between amyloid fibril formation/clearance and aberrant lipid interactions are still unavailable. Recently, many studies have described the key role played by membrane bound Aβ assemblies in neurotoxicity. Moreover, it has been suggested that a derangement of the ubiquitin proteasome pathway and autophagy is significantly correlated with toxic Aβ aggregation and dysregulation of lipid levels. Thus, studies focusing on the role played by lipids in Aβ aggregation and proteostasis could represent a promising area of investigation for the design of valuable treatments. In this review we examine current knowledge concerning the effects of lipids in Aβ aggregation and degradation processes, focusing on the therapeutic opportunities that a comprehensive understanding of all biophysical, biochemical, and biological processes involved may disclose.