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.

阿尔茨海默病 (AD) 的特征在于大脑中 Aβ 肽的淀粉样沉积物的积累。除了遗传背景，其他疾病的存在和不健康的生活方式也是 AD 发展的已知风险因素。尽管越来越多的临床证据表明脂质代谢受损与 Aβ 沉积有关，但仍然无法获得有关淀粉样蛋白原纤维形成/清除与异常脂质相互作用之间联系的机制见解。最近，许多研究描述了膜结合 Aβ 组装在神经毒性中的关键作用。此外，有人提出泛素蛋白酶体途径和自噬的紊乱与毒性 Aβ 聚集和脂质水平失调显着相关。因此，关注脂质在 Aβ 聚集和蛋白质稳态中所起作用的研究可能代表一个有希望的研究领域，用于设计有价值的治疗方法。在这篇综述中，我们研究了当前关于脂质在 Aβ 聚集和降解过程中的影响的知识，重点关注全面了解所涉及的所有生物物理、生物化学和生物过程可能会揭示的治疗机会。