Abstract/Summary

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. Alzheimer’s disease (AD) is one of the greatest challenges facing humanity today. It is the most common cause of dementia, accounting for around two-thirds of cases [1], with a global prevalence of around 24,000,000 people [2], mostly in Western countries, a figure that is growing as life expectancy continues to rise around the world [3]. There are currently no treatments that will prevent people getting the disease [4, 5], and current treatments can only delay disease progression by several months at best [6]. 99% of drug trials have failed [7], and many large pharmaceutical companies have abandoned research into AD therapies [8]. Why have we made so little progress in treating AD? An increasing number of researchers are arguing that it is because the current predominant explanation, the amyloid hypothesis, does not fully account for the disease [6, 9–11]. This paper argues that there is increasing evidence that the Lipid Invasion Model is a viable alternative hypothesis for AD.