One of the most common forms of dementia in the Western world is Alzheimer’s disease. It has been generally accepted that amyloid-B protofibrils is the most likely cause for the disease. Until now, the conditions under which this type of protofibril is formed and leads to the disease remained unknown.
Researchers at Vrije University, Brussels (VIB), have discovered that certain lipids, present 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 a cell depends on the right folding of thousands of proteins. Cells normally correct misfolded proteins. However with diseases, such as Alzheimer’s, Parkinson’s, and Creutzfeldt-Jacob’s, the misfolded proteins are not corrected and instead are deposited in the body’s tissues. In the case of Alzheimer’s disease the misfolding of the amyloid-B protein leads in various stages to the formation of plaques. These plaques consist of an accumulation of fibrils, which are not toxic. One of the intermediary stages in the formation of plaques is the formation of the protofibril form of amyloid-B peptide. Protofibrils are toxic for brain cells, causing the poisoned cells to die off and leads to memory loss, which 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. 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.