Caffeine has a positive effect on neurofibrillary tangles that form in the brain of Alzheimer’s patients, i.e. clusters of pathologically altered tau proteins, determined a Franco-German research team.
Their groundbreaking discovery is featured in the latest issue of Neurobiology of Aging.
The team led by Dr. Christa E. Müller from the University of Bonn and Dr. David Blum from the University of Lille for the first time in history showed that the use of caffeine, in the amount corresponding to the dose contained in two cups of coffee, can significantly slow down the progression of the disease.
The tau protein is a protein characteristic of nerve cells, which, thanks to its ability to bind to microtubules, is responsible for the formation of the cytoskeleton of cells and ensuring its stability. Under normal conditions, it undergoes phosphorylation with the participation of protein kinases, which determines its activity.
However, it happens that the phosphorylation of the tau protein becomes too strong, which leads to pathological changes in its structure. Instead of attaching to microtubules, the protein particles start to form aggregates (deposits) called neurofibrillary tangles. Their accumulation leads to disruption of communication between neurons, disturbances in their functioning and – as a result – cell death. Tau tangles – along with beta-amyloid plaques – are the most characteristic feature of Alzheimer’s disease.
Despite intense research over the years, scientists have yet to find a cure that can stop the formation of tangles and prevent them from accumulating in the brain. Thanks to the research by Blum and Müller, this can change.
The researchers designed an experiment involving mice with a genetically modified version of the tau gene, producing an abnormal form of the tau protein – one that tends to form tangles. The animals were divided into two groups: the control group, which was given a placebo, and the other group, which was given a small amount of caffeine for several weeks – 0,3 grams for each liter of drinking water. This is the amount of caffeine in two cups of coffee in humans.
It turned out that mice regularly taking caffeine performed much better in memory tests. Imaging studies also showed a much lower accumulation of harmful tau tangles in the brains of these animals compared to the control group.
Scientists explain that this is the result of the antagonistic effect of caffeine on various adenosine receptors in the brain. In this case, the receptor called A2A is particularly important.
Our research is a giant step forward, says Dr. Müller. – The results we have obtained are really promising. We were the first to show that A2A receptor antagonists (i.e. compounds like caffeine) can slow disease progression and protect the brain from neurofibrillary tangles. And the side effects from their use are small.
Scientists now want to confirm the positive effects of caffeine (and synthetic A2A antagonists) in other animal models. If the results are as expected, human clinical trials can begin. “Of course, you need to be patient, as it will be a long time before A2A antagonists are considered new therapeutic agents for Alzheimer’s disease, but we are optimistic,” says Müller. (PAP)