Alzheimer’s disease (AD) is the most common cause of dementia, and its underlying mechanisms have been a subject of great interest. The mainstream theory of AD pathology suggests that the disease is primarily associated with tau protein and amyloid-beta (Aβ). However, an increasing body of research has revealed that abnormalities in lipid metabolism may be an important event throughout the pathophysiology of AD. Astrocytes, as important members of the lipid metabolism network in the brain, play a significant role in this event. The study of abnormal lipid metabolism in astrocytes provides a new perspective for understanding the pathogenesis of AD. This review focuses on the abnormal metabolism of fatty acids (FAs) and cholesterol in astrocytes in AD, and discusses it from three perspectives: lipid uptake, intracellular breakdown or synthesis metabolism, and efflux transport. We found that, despite the accumulation of their own fatty acids, astrocytes cannot efficiently uptake fatty acids from neurons, leading to fatty acid accumulation within neurons and resulting in lipotoxicity. In terms of cholesterol metabolism, astrocytes exhibit a decrease in endogenous synthesis due to the accumulation of exogenous cholesterol. Through a thorough investigation of these metabolic abnormalities, we can provide new insights for future therapeutic strategies by literature review to navigate this complex metabolic maze and bring hope to patients with Alzheimer’s disease.

中文翻译：

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穿越代谢迷宫：阿尔茨海默氏星形胶质细胞中脂肪酸和胆固醇过程的异常

阿尔茨海默氏病（AD）是痴呆症最常见的原因，其潜在机制一直是人们非常感兴趣的课题。 AD病理学的主流理论认为，该疾病主要与tau蛋白和β淀粉样蛋白（Aβ）有关。然而，越来越多的研究表明，脂质代谢异常可能是整个 AD 病理生理学的一个重要事件。星形胶质细胞作为大脑脂质代谢网络的重要成员，在此事件中发挥着重要作用。星形胶质细胞脂质代谢异常的研究为理解AD的发病机制提供了新的视角。本文重点关注AD中星形胶质细胞脂肪酸（FAs）和胆固醇代谢异常，并从脂质摄取、细胞内分解或合成代谢以及外排转运三个角度进行讨论。我们发现，尽管星形胶质细胞自身积累了脂肪酸，但它无法有效地从神经元中摄取脂肪酸，导致脂肪酸在神经元内积累并导致脂毒性。在胆固醇代谢方面，星形胶质细胞由于外源胆固醇的积累而表现出内源合成的减少。通过对这些代谢异常的深入研究，我们可以通过文献综述为未来的治疗策略提供新的见解，以导航这个复杂的代谢迷宫，为阿尔茨海默病患者带来希望。