TREM2 gene carries benefits as well as risks in Alzheimer’s disease

10 October 2017

Researchers at the Washington University School of Medicine have studied the role of the Alzheimer’s risk gene TREM2, finding surprising evidence that the gene could also be protective against damage caused by tau tangles – a key hallmark of the disease. The results are published in the journal Proceedings of the National Academy of Sciences.

Alzheimer’s disease is the most common cause of dementia, affecting 500,000 people in the UK alone, with symptoms usually including the gradual loss of memory and communication skills.

TREM2 is a risk gene in the development of Alzheimer’s disease, discovered by Alzheimer’s Research UK-funded scientists in 2012. It’s discovery has led to an explosion of research to understand the gene, how it works and why it may put people at higher risk of Alzheimer’s. Scientists studying the early stages of the disease have found that a loss of TREM2 can reduce the immune system’s ability to protect the brain from amyloid, a key protein associated with Alzheimer’s.

In this study, researchers set out to investigate what impact a loss of TREM2 may have on damage caused by the tau protein – a second hallmark protein involved in Alzheimer’s and other forms of dementia. To do this, they used mice bred to show a build-up of tau tangles in the brain and compared those mice with normal TREM2, to mice where the TREM2 gene had been switched off.

To their surprise, the team discovered that later in Alzheimer’s disease, when the toxic tangles tau are present in the brain, the absence of TREM2 protein seems to protect the brain from further damage. Mice without the TREM2 gene had lower levels of inflammation in the brain and were protected against brain cell loss driven by the tau protein.

The authors suggest that the normal TREM2 protein could have a dual role in the brain, protecting against damage driven by amyloid in its normal form, but also acting to drive damaging processes caused by tau.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK said:

“Natural differences in our genes give rise to different proteins and it is these small differences that make us all unique. While most of the genetic differences between us are completely benign, some can lead to changes in our risk of diseases, including Alzheimer’s.”

“This is interesting early research into TREM2, an important genetic risk factor for Alzheimer’s. The findings add to a growing body of evidence showing that our immune system is involved in the development of Alzheimer’s disease, but highlight the challenge of working with such a complex biological process. Understanding the complex role of the immune system in Alzheimer’s is critical for shaping future treatment approaches, and can only be realised through continued investment in research.”

“While we cannot change our genes, there are some lifestyle changes we can make that could help to reduce our risk of conditions such as dementia. The saying goes that what is good for the heart is good for the brain. Eating a healthy, balanced diet, keeping physically active, not smoking, only drinking in moderation, keeping cholesterol and blood pressure in check, and maintaining a healthy weight are all ways we can look after our brains in later life.”