4.5 Article

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

期刊

JOURNAL OF ALZHEIMERS DISEASE
卷 94, 期 2, 页码 457-470

出版社

IOS PRESS
DOI: 10.3233/JAD-221175

关键词

Alzheimer's disease; amyloid; apolipoproteins; blood-brain barrier; cholesterol; ethanol; lipids; lipoproteins; neurofibrillary tangles; nonesterified fatty acids; plaque

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The Lipid Invasion Model (LIM) proposes that Alzheimer's disease (AD) is caused by external lipid invasion to the brain following damage to the blood-brain barrier (BBB). This hypothesis explains the observed neuropathologies and risk factors associated with AD, emphasizing the role of cholesterol and fatty acids instead of amyloid-beta. The LIM offers new perspectives for the diagnosis, prevention, and treatment of AD, and may also shed light on other neurodegenerative diseases.
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 newevidence 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-beta (A beta) but bad cholesterol and free fatty acids, let into the brain by a damaged BBB. It suggests that the focus on A beta 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.

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