Alzheimer’s Brain Barrier Damage Theory Could Pave Way for New Treatments

Summary: Lipids entering the brain as a result of damage to the blood-brain barrier may be a determining cause of Alzheimer’s disease. Researchers say simple lifestyle changes could reduce Alzheimer’s risks by reducing the impact on the BBB and decreasing Alzheimer’s associated brain damage.

Source: University of Reading

Alzheimer’s Disease could be caused by damage to a protective barrier in the body that allows fatty substances to build up in the brain, newly published research argues.

A new explanation called the ‘Lipid Invasion Model’, argues that lipids entering the brain due to damage to the blood brain barrier – a dense system of small blood vessels in the brain that allow only a small number of essential substances to pass through – is the determining cause of the degenerative disease that affects millions worldwide.

The hypothesis is published in the Journal of Alzheimer’s Disease Reports and could open up new diagnosis or treatment possibilities. The theory also supports the idea that certain lifestyle changes could reduce the risk of Alzheimer’s Disease by reducing the impact on the blood brain barrier and the resulting damage to the brain seen in people with Alzheimer’s.

Dr Jonathan Rudge, Postdoctoral researcher at the University of Reading and author of the study said: “A healthy blood brain barrier is incredibly important to how our brains function effectively. If the barrier gets damaged, as is the case with people who develop Alzheimer’s, external lipids like cholesterol and fatty acids get a chance to pass through.

“These external lipids are managed differently to those typically found within the brain. My theory proposes that these invading lipids are resulting in brain damage, like brain shrinkage, and development of amyloid plaques and ‘tau tangles’, which causes the behaviours characteristic of Alzheimer’s, such as memory loss, sleep disorders and paranoia.”

The presence of excess lipids in the brain cells of Alzheimer’s patients is an element of Alois Alzheimer’s original published research in 1906, but there has been relatively little research into it since.

The new study brings together previous research to present the fresh explanation of the disease’s cause.  It follows 10 years of research and suggests that risk factors commonly associated with Alzheimer’s Disease are the same factors that damage the blood brain barrier – old age, head injury, hypertension, smoking, obesity, diabetes, chronic sleep deprivation and stress.

It suggests that this is the reason footballers and boxers are particularly at risk, and why the disease affects largely older people, because in both cases the blood brain barrier has been damaged or worn away.

There are two types of Alzheimer’s – the comparatively rare, inherited, early-onset form and the non-inherited, late-onset form, associated with ageing. This latter form is becoming more and more common as people live longer but the current explanation known as the amyloid hypothesis relates more to the rarer inherited form.

This shows the outline of a head filled with cogwheels and a lightbulb
The presence of excess lipids in the brain cells of Alzheimer’s patients is an element of Alois Alzheimer’s original published research in 1906, but there has been relatively little research into it since. Image is in the public domain

This explanation states that the disease is caused by excess levels of a protein called beta-amyloid.  The Lipid Invasion Model supports this up to a point but argues that, in the late-onset form, beta-amyloid is just one of a number of factors that damage the blood brain barrier, allowing external lipids in.

The Lipid Invasion Model opens up new pathways for research into the detection, prevention and treatment of the disease. It could have parallels in other neurodegenerative diseases, such as Parkinson’s and Motor Neurone Disease, which also disproportionately affect older people and people engaged in certain sports, and might also be associated with damage to the blood brain barrier.


Alois Alzheimer (1864-1915) was the German psychiatrist and neuropathologist credited with identifying the first published case of ’presenile dementia’, later identified as Alzheimer’s disease. His was the first description of the strange behavioural symptoms (poor short-term memory, sleep disturbance and paranoia) and brain pathology (brain shrinkage and the presence of amyloid plaques and neurofibrillary tangles) commonly associated with the disease.

Alzheimer’s disease is the most common form of dementia affecting 24 million people, mostly in the western world. There is now a one in three chance that we will get it in old age.

About this Alzheimer’s disease research news

Author: Peter Bryant
Source: University of Reading
Contact: Peter Bryant – University of Reading
Image: The image is in the public domain

Original Research: Open access.
A New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model” by Jonathan Rudge et al. Journal of Alzheimer’s Disease Reports


A New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model

This paper proposes a new hypothesis for Alzheimer’s disease (AD)—the lipid invasion model. It argues that AD results from external influx of free fatty acids (FFAs) and lipid-rich lipoproteins into the brain, following disruption of the blood-brain barrier (BBB).

The lipid invasion model explains how the influx of albumin-bound FFAs via a disrupted BBB induces bioenergetic changes and oxidative stress, stimulates microglia-driven neuroinflammation, and causes anterograde amnesia.

It also explains how the influx of external lipoproteins, which are much larger and more lipid-rich, especially more cholesterol-rich, than those normally present in the brain, causes endosomal-lysosomal abnormalities and overproduction of the peptide amyloid-β (Aβ). This leads to the formation of amyloid plaques and neurofibrillary tangles, the most well-known hallmarks of AD.

The lipid invasion model argues that a key role of the BBB is protecting the brain from external lipid access. It shows how the BBB can be damaged by excess Aβ, as well as by most other known risk factors for AD, including aging, apolipoprotein E4 (APOE4), and lifestyle factors such as hypertension, smoking, obesity, diabetes, chronic sleep deprivation, stress, and head injury.

The lipid invasion model gives a new rationale for what we already know about AD, explaining its many associated risk factors and neuropathologies, including some that are less well-accounted for in other explanations of AD.

It offers new insights and suggests new ways to prevent, detect, and treat this destructive disease and potentially other neurodegenerative diseases.

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