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

Alzheimer's Diseases (AD) is characterized by the accumulation of amyloid deposits of A beta 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 A beta 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 A beta assemblies in neurotoxicity. Moreover, it has been suggested that a derangement of the ubiquitin proteasome pathway and autophagy is significantly correlated with toxic A beta aggregation and dysregulation of lipid levels. Thus, studies focusing on the role played by lipids in A beta 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 A beta aggregation and degradation processes, focusing on the therapeutic opportunities that a comprehensive understanding of all biophysical, biochemical, and biological processes involved may disclose.

Automated summary

Alzheimer's Disease (AD) is characterized by amyloid deposits in the brain, with factors such as genetic background, other diseases, and lifestyle contributing to its development. Recent studies suggest a link between impaired lipid metabolism and A beta deposition, with membrane-bound A beta assemblies playing a key role in neurotoxicity. Additionally, dysregulation of lipid levels and toxic A beta aggregation may be linked to derangements in cellular pathways such as ubiquitin proteasome and autophagy. Understanding the role of lipids in A beta aggregation and proteostasis could lead to valuable treatment options.