q&more
My watch list
my.chemie.de  
Login  

News

Defective immune cells in the brain cause Alzheimer’s disease

Scientists are studying the role of immune cell activation in Alzheimer's disease

GDJ, pixabay.com, CC0

09-Jan-2019: Mutations of the TREM2 gene can significantly increase the risk of Alzheimer's disease. Scientists from the German Center for Neurodegenerative Diseases (DZNE) and the Ludwig-Maximilians-University Munich now shed light on the reasons why TREM2 is so important for brain health. They show that TREM2 activates brain immune cells to eliminate toxic deposits, first and foremost in the early stages of the disease. The study is published in the journal “Nature Neuroscience” and has important implications for the development of new drugs.

A hallmark of Alzheimer's disease is the formation of toxic deposits in the brain, so-called plaques. Specialized immune cells termed microglia protect the brain by clearing it from these toxic debris. TREM2 is a key factor in activating microglia and thus serves as an important target for novel therapeutic approaches. To further explore these therapeutic options, the Munich scientists undertook a detailed analysis of disease development in mice with and without a functional TREM2 gene.

In mice with healthy TREM2, microglia cluster around small emerging plaques early in the disease process and prevent them from enlarging or spreading. "We were able to show that microglia are specifically attracted to amyloid plaques. They surround individual plaques and engulf them piece by piece," explains lead investigator Christian Haass, speaker of the DZNE's Munich site, and a professor at the Ludwig-Maximilians-University Munich. In contrast, in mice lacking TREM2, microglia were unable to carry out this important task. Therapeutic activation of TREM2 in an early stage of the disease could thus help counteract the formation of toxic amyloid-beta protein aggregates.

However, the study results also call for caution when implementing such a therapy. While TREM2 prevents plaque formation early in disease progression, it may have the opposite effect later on. In more advanced stages of the disease, the plaques grew faster in mice with functional TREM2 than in mice lacking the corresponding gene. The researchers discovered that this could be explained by the fact that TREM2 induces microglia to produce a substance called ApoE, which enhances aggregate formation. "Our study shows that we have to be extremely careful and investigate a new therapeutic approach thoroughly in animal models before testing it on humans," says Haass. "According to our findings, it could have dramatic consequences if we over-activate microglia."

"In the future, it will be important to treat Alzheimer’s disease in a stage-specific manner," Haass explains. According to the present study, for example, activating microglia via TREM2 would be a strategy that should be applied early in disease progression. Haass and his colleagues are currently working on the development of antibodies that stabilize TREM2 and thereby activate microglia. The scientists are now using several animal models and different experimental approaches to test possible therapeutic strategies and combination therapies with other drugs.

"All important genetic alterations that increase the risk of Alzheimer's disease lead to changes in plaque formation," Haass explains. This suggests that these protein aggregates are the cause of the disease. The current study provides hope that it is possible to counteract plaque formation by activating TREM2, and at the same time highlights potential risks that scientists need to take into account when pursuing such an approach.

Original publication:
Parhizkar et al.; "Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE"; Nature Neuroscience; 2019

Facts, background information, dossiers

  • Alzheimer's disease
  • immune cells
  • gene mutations
  • microglia
  • protein aggregates
  • plaques

More about LMU

  • News

    One transistor for all purposes

    In mobiles, fridges, planes – transistors are everywhere. But they often operate only within a restricted current range. LMU physicists have now developed an organic transistor that functions perfectly under both low and high currents. Transistors are semiconductor devices that control volt ... more

    Tiny “blinkers” reveal molecules inside cells

    LMU physicists led by Ralf Jungmann introduce an entirely new approach to super-resolution microscopy: Tiny ‘blinkers’ enable simultaneous imaging of multiple biomolecules. In everyday life, blinking lights can send signals – for example, that a car is going to turn. Now, researchers have e ... more

    Solid-state catalysis: Fluctuations clear the way

    LMU chemists have identified a mechanism that allows molecules to diffuse rapidly on the already crowded surface of a solid-state catalyst – an important capability, especially for efficient catalysis under industrial conditions. The use of efficient catalytic agents is what makes many tech ... more

  • Authors

    Prof. Dr. Thomas Carell

    Thomas Carell graduated in chemistry, completing his doctorate at the Max Planck Institute for Medical Research under the tutelage of Prof. Dr Dr H. A. Staab. Following a research position in the USA, he accepted a position at ETH Zurich, setting up his own research group in the Laboratory ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by:



Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE