The brain’s immune cells can be activated to slow Alzheimer’s disease

Overview: Activating TREM2 on microglia in the brains of people with Alzheimer’s disease could slow the progression of the neurodegenerative disease.

Source: University of Lund

The brain’s big-eating immune cells may slow the progression of Alzheimer’s disease.

This is according to a study published in Nature aging.

The brain’s own immune cells are called microglia and are located in the central nervous system. They are big feeders, killing viruses, damaged cells and infectious agents they encounter. It has long been known that microglial cells can be activated in different ways in various neurological disorders such as Alzheimer’s and Parkinson’s disease.

Depending on how they are activated, they can either stimulate or slow the development of disease. Researchers from Lund University and the Karolinska Institutet have now shown that a certain type of activation of the microglial cells triggers inflammatory defense mechanisms in the immune system.

“Most people probably think that inflammation in the brain is a bad thing and that you have to slow down the inflammation system in case of illness. But inflammation doesn’t just have to be negative,’ says Joana B. Pereira, a researcher at Lund University and at the Karolinska Institutet, the first author of the study.

One of the proteins found on the surface of microglial cells is TREM2. When an unusual mutation occurs in this protein, the risk of developing Alzheimer’s disease increases. However, when the protein is activated, it may instead be protective. This is because the TREM2 receptor appears to detect residual products from disintegrating cells in the brain, activating it.

When TREM2 is activated in people with Alzheimer’s disease, the researchers found that less of the thread-like structures formed by the protein tau accumulate in brain cells.

This shows a brain
The brain’s own immune cells are called microglia and are located in the central nervous system. The image is in the public domain

“This in turn means that the development of the disease is slower and the deterioration of the patient’s cognitive abilities is delayed,” says Oskar Hansson, a professor of neurology at Lund University and a senior physician at Skåne University Hospital.

It has been previously observed in some animal studies that microglial cells can eat tau proteins and thus clean up what is abnormal in the brain. Oskar Hansson believes this could be the cause of whatever happens in this study, which is being conducted in humans.

Oskar Hansson also finds the results of the study particularly interesting, as several pharmaceutical companies are now developing antibodies that can activate TREM2 in particular, and he hopes for a future treatment method for Alzheimer’s disease.

“In addition to looking for therapies to reduce the proteins beta-amyloid and tau, I see this as a third treatment principle. In the future, patients may be able to receive a cocktail of drugs that, in addition to reducing beta-amyloid, also enhance the TREM2 antibodies and thus slow down the course of the disease,” concludes Oskar Hansson.

About this news about Alzheimer’s disease

Author: Press Office
Source: University of Lund
Contact: Press Service – University of Lund
Image: The image is in the public domain

Original research: Open access.
“Microglial activation protects against tau aggregate accumulation in non-demented individuals with underlying pathology of Alzheimer’s disease” by Joana B. Pereira et al. Nature aging

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Abstract

Microglial activation protects against tau aggregate accumulation in non-demented individuals with underlying pathology of Alzheimer’s disease

The role of microglia in tau accumulation is currently unclear, but could provide important insight into the mechanisms underlying Alzheimer’s disease (AD).

Here we measured the microglial marker soluble TREM2 and the disease-associated microglial activation stage 2 markers AXL, MERTK, GAS6, LPL, CST7, SPP1 and CSF1 in non-demented subjects from the Swedish BioFINDER-2 cohort undergoing longitudinal tau positron emission tomography. underwent. (PET), amyloid-PET and global cognitive assessment.

To assess whether baseline microglial markers had an effect on AD-related changes, we studied three subgroups of individuals: 121 with evidence of amyloid PET pathology (A+), 64 with additional evidence of tau-PET pathology (A+T+) and 159 without amyloid or tau PET pathology (AT).

Our results showed that increased levels of TREM2 were associated with slower amyloid accumulation in A+ individuals in addition to slower tau deposition and cognitive decline in A+T+ subjects. Similarly, higher levels of AXL, MERTK, GAS6, LPL, CST7, and CSF1 predicted slower tau accumulation and/or cognitive decline in the A+T+ group.

These findings have important implications for future therapeutic strategies aimed at stimulating microglial protective functions in AD.

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