‘Lack of cleaning’ in brain cells is central to Alzheimer’s disease

An international research team with representation from the University of Copenhagen has created a better understanding of Alzheimer’s. They have shown that the cleaning system of the brain cells, the so-called mitophagy, is very weakened in animals and humans with Alzheimer’s. And when they improve the cleaning system in the animals, the Alzheimer’s symptoms almost disappear.

Scientists around the world are still struggling to understand Alzheimer’s better in order to be able to treat and potentially prevent the development of the debilitating disease in the future. No new medications have been approved during recent years.

In a new study in the scientific journal Nature Neuroscience, an international team of researchers from the University of Copenhagen, National Institutes of Health and the University of Oslo among others have come closer to a new way of attacking the disease. They target the efforts towards the cleaning process in the brain cells called mitophagy.

‘When the cleaning system does not work properly, there will be an accumulation of defective mitochondria in the brain cells. And this may be really dangerous. At any rate, the poor cleaning system is markedly present in cells from both humans and animals with Alzheimer’s. And when we improve the cleaning in live animals, their Alzheimer’s symptoms almost disappear,’ says Vilhelm Bohr, author of the study and affiliate professor at the Center for Healthy Aging and National Institutes of Health.

Defect Energy Factories
The researchers have looked more closely at the cleaning process in brain cells from deceased Alzheimer’s patients, in Alzheimer’s-induced stem cells and in live mice and roundworms with Alzheimer’s. In addition, they have also tested active substances targeted at the cleaning process in the animal models.

‘It significantly strengthens our results that the cleaning process seems to be important in both human cells and across different animal species. And then it is encouraging that in living animals we are able to improve the central Alzheimer’s symptoms, memory and learning,’ says Vilhelm Bohr.

The mitochondria lie inside the cell and can be seen as the cell’s energy factories. Mitophagy breaks down defective mitochondria and reuses the proteins that they consist of. It is known from previous research that dysfunctional mitophagy is associated with poor function and survival of nerve cells, but so far, the connection with Alzheimer’s is unclear.

Slowing Down the Accumulation
In both Alzheimer’s and other states of dementia, there is an accumulation of the proteins tau and beta amyloid in the brain, leading to cell death. In the new animal models, the researchers show that when boosting the mitophagy, such accumulation will slow down.

The researchers believe that altogether their findings indicate that the cleaning process is a potential target for the treatment of Alzheimer’s, which should be further investigated. They therefore plan to start clinical trials in humans in the near future.

The study is supported by Helse Sør Øst RHF (the Southern and Eastern Norway Regional Health Authority), the Research Council of Norway, the ERC and the Olav Thon Foundation.

The research at the Center for Healthy Aging is supported by Nordea-Fonden.

The researchers behind the study have a research and development agreement with ChromaDex and Elysium Health.

Read the entire study ‘Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease’ in Nature Neuroscience.

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