Lipids in the brain an important factor for Alzheimer's disease?

December 10, 2007

As the most common form of dementia in the Western world, Alzheimer's disease carries enormous implications for our ageing society. It is generally accepted that the disease is caused by Alzheimer peptide (A -peptide) protofibrils. Until now, the conditions under which this type of protofibril is formed and leads to the disease remained unknown. VIB researchers have now discovered that certain lipids, present also in our brains, promote the formation of this protofibril.

This discovery is of major importance because it opens up new avenues of research into finding medicines against Alzheimer's disease. It also explains earlier indications of a link between lipids and Alzheimer's disease.

The biological functioning of cells depends on the right folding of thousands of proteins. Normally, cells automatically correct misfolded proteins. In diseases such as Alzheimer’s, Parkinson's and Creutzfeld-Jacob's, however, misfolded proteins are deposited in the body's tissues.

In Alzheimer's disease – the most common form of dementia, which in Belgium alone affects about 100,000 people – misfolding of the A -amyloid peptide leads in various stages to the formation of plaques. These plaques consist of accumulations of so-called fibrils and is not in itself toxic. One of the intermediary stages in the formation of plaques is the formation of the protofibril form of the A -peptide. Protofibrils are toxic for brain cells, causing the poisoned cells to die off and leading to memory loss. This is why these protofibrils are considered to be the main cause of the symptoms of Alzheimer's disease.

VIB researchers were able, using certain lipids, to convert the fibrils into protofibrils. This came as a surprise, for it had long been assumed that the fibrils – and the plaque they cause – are stable and that once they have formed they cannot disappear or be transformed into another structure. Ivo Martins, Joost Schymkowitz and Frederic Rousseau (VIB, Vrije Universiteit Brussel), and Inna Kupperstein and Bart De Strooper (VIB, K.U.Leuven) have shown that certain lipids normally occurring in the brain can destabilize the fibrils, and therefore also the plaque that is so typical of Alzheimer's disease.

The liberated protofibrils are toxic for brain cells, causing them to die off – at least in vitro. The researchers were able to show that this also happens in vivo by injecting laboratory animals (mice) with the protofibrils. This caused memory loss in the mice. The researchers explain that these symptoms are comparable with those of early stage dementia in humans.

The discovery opens up a new avenue of research into possible medicines against Alzheimer's disease. It indicates that substances that neutralize the toxicity or the formation of protofibrils might be able to be used as medicines against Alzheimer's disease. With the discovery of a method for producing toxic protofibrils, the researchers at the VIB have provided a good model for finding medicines that could counteract the formation of protofibrils.

Their research also indicates that the concentration of lipids in the brain greatly influences the biological equilibrium between non-toxic plaques and toxic oligomeres. These results open up new avenues of research into the effects of fat metabolism for diseases such as Alzheimer's.

Source: VIB (the Flanders Institute for Biotechnology)

Explore further: Antibody provide a more exact Alzheimer's diagnosis radioactive tracers

Related Stories

Antibody provide a more exact Alzheimer's diagnosis radioactive tracers

February 19, 2016
For the first time, researchers have succeeded in passing an antibody through the blood-brain barrier to act as a tracer for PET imaging of the brain. This resulted in more precise information being obtained than with regular ...

Research yields first detailed view of morphing Parkinson's protein

September 6, 2013
(Medical Xpress)—Researchers have taken detailed images and measurements of the morphing structure of a brain protein thought to play a role in Parkinson's disease, information that could aid the development of medications ...

Recommended for you

Past encounters with the flu shape vaccine response

February 20, 2018
New research on why the influenza vaccine was only modestly effective in recent years shows that immune history with the flu influences a person's response to the vaccine.

Building better tiny kidneys to test drugs and help people avoid dialysis

February 16, 2018
A free online kidney atlas built by USC researchers empowers stem cell scientists everywhere to generate more human-like tiny kidneys for testing new drugs and creating renal replacement therapies.

Expanding Hepatitis C testing to all adults is cost-effective and improves outcomes

February 16, 2018
According to a new study, screening all adults for hepatitis C (HCV) is a cost-effective way to improve clinical outcomes of HCV and identify more infected people compared to current recommendations. Using a simulation model, ...

Study suggests expanded range for emerging tick-borne disease

February 16, 2018
Human cases of Borrelia miyamotoi, a tick-borne infection with some similarities to Lyme disease, were discovered in the eastern United States less than a decade ago. Now new research led by the Yale School of Public Health ...

Flu shot only 36 percent effective, making bad year worse (Update)

February 15, 2018
The flu vaccine is doing a poor job protecting older Americans and others against the bug that's causing most illnesses.

IFN-mediated immunity to influenza A virus infection influenced by RIPK3 protein

February 15, 2018
Each year, influenza kills half a million people globally with the elderly and very young most often the victims. In fact, the Centers for Disease Control and Prevention reported 37 children have died in the United States ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.