'Lack Of Cleaning' in Brain Cells Is Central to Alzheimer's Disease

‘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, no connection with Alzheimer’s has been shown.

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.

Contacts and sources:
Vilhelm Bohr / Mathias Traczyk
University of Copenhagen The Faculty of Health and Medical Sciences

Citation: ‘Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease’
Evandro F. Fang, Yujun Hou, Konstantinos Palikaras, Bryan A. Adriaanse, Jesse S. Kerr, Beimeng Yang, Sofie Lautrup, Md Mahdi Hasan-Olive, Domenica Caponio, Xiuli Dan, Paula Rocktäschel, Deborah L. Croteau, Mansour Akbari, Nigel H. Greig, Tormod Fladby, Hilde Nilsen, M. Zameel Cader, Mark P. Mattson, Nektarios Tavernarakis & Vilhelm A. Bohr
Nature Neuroscience (2019) http://dx.doi.org/10.1038/s41593-018-0332-9

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