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脂质入侵模型:阿尔茨海默病新解释的不断增加的证据。

The Lipid Invasion Model: Growing Evidence for This New Explanation of Alzheimer's Disease.

机构信息

School of Biological Sciences, University of Reading, Berks, UK.

出版信息

J Alzheimers Dis. 2023;94(2):457-470. doi: 10.3233/JAD-221175.

Abstract

The Lipid Invasion Model (LIM) is a new hypothesis for Alzheimer's disease (AD) which argues that AD is a result of external lipid invasion to the brain, following damage to the blood-brain barrier (BBB). The LIM provides a comprehensive explanation of the observed neuropathologies associated with the disease, including the lipid irregularities first described by Alois Alzheimer himself, and accounts for the wide range of risk factors now identified with AD, all of which are also associated with damage to the BBB. This article summarizes the main arguments of the LIM, and new evidence and arguments in support of it. The LIM incorporates and extends the amyloid hypothesis, the current main explanation of the disease, but argues that the greatest cause of late-onset AD is not amyloid-β (Aβ) but bad cholesterol and free fatty acids, let into the brain by a damaged BBB. It suggests that the focus on Aβ is the reason why we have made so little progress in treating the disease in the last 30 years. As well as offering new perspectives for further research into the diagnosis, prevention, and treatment of AD, based on protecting and repairing the BBB, the LIM provides potential new insights into other neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis/motor neuron disease.

摘要

脂质入侵模型(LIM)是阿尔茨海默病(AD)的一个新假说,该假说认为 AD 是由于血脑屏障(BBB)损伤后外部脂质入侵大脑引起的。LIM 全面解释了与该疾病相关的观察到的神经病理学,包括 Alois Alzheimer 本人首次描述的脂质异常,并解释了现在与 AD 相关的广泛的风险因素,所有这些因素也与 BBB 损伤有关。本文总结了 LIM 的主要论点,以及支持该假说的新证据和论点。LIM 包含并扩展了淀粉样蛋白假说,该假说目前是对该疾病的主要解释,但认为晚发性 AD 的最大原因不是淀粉样蛋白-β(Aβ),而是坏胆固醇和游离脂肪酸,它们通过受损的 BBB 进入大脑。它表明,之所以在过去 30 年中我们在治疗这种疾病方面进展甚微,是因为我们过于关注 Aβ。除了为基于保护和修复 BBB 的 AD 的诊断、预防和治疗提供新的研究视角外,LIM 还为帕金森病和肌萎缩侧索硬化症/运动神经元病等其他神经退行性疾病提供了潜在的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7856/10357195/23596573cbd5/jad-94-jad221175-g001.jpg

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