Neurology Central

TREM2 gene simultaneously a benefit and a hazard for Alzheimer’s sufferers

Research recently published in the Proceedings of the National Academy of Sciences has suggested that in the early stages of Alzheimer’s, TREM2 variants can impede the immune system’s ability to protect the brain from amyloid beta; while in later stages coinciding with a buildup of tau tangles, the absence of TREM2 protects the brain from damage. The study was conducted by researchers from Washington University School of Medicine in St. Louis (MO, USA).

In an investigation into the effects of TREM2 on tau, it was discovered that mice without the protein displayed significantly reduced brain damage in comparison to those with it, as the absence of TREM2 impacts microglia’s capacity to generate the energy necessary to limit the spread of amyloid beta plaques, in turn raising the risk of tau tangles.

All genetically modified mice carried a mutant form of human tau prone to forming tangles. While there was no difference in the amount of TREM2 tangles between the two groups, after the removal of the TREM2 gene, researchers demonstrated that only some carried the protein in their microglia. At 9 months of age the brains of mice with TREM2 were noticeably diminished, particularly in areas important to memory. It was notable that there was significantly less damage in the mice without TREM2.

Researchers in the field of Alzheimer’s have already been developing methods of targeting TREM2, but the new data now raises the question of whether it is more beneficial to stimulate or inhibit the protein. For years prevention and treatment of Alzheimer’s has focused on targeting amyloid plaques and tau tangles but no therapy has yet been proven effective. After the discovery of TREM2’s risk factor 4 years ago, scientists were presented with a novel approach to tackling the disease.

The findings suggest that microglia can inhibit or promote neurological damage in Alzheimer’s, demonstrating a previously unsuspected complexity in treating the disease. “You might want to activate microglia early on, when people are just beginning to collect amyloid,” senior author David Holtzman (Washington University School of Medicine, St. Louis, MO, USA) summarized.

“If they’re already developing symptoms, then they’re later in the disease process, so you’d probably want to suppress microglia. However, these ideas would need to be thoroughly tested in animal models before we start talking about taking it into people,” Holtzman concluded.


Leyns C, Ulrich J, Finn M et al. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc. Natl. Acad. Sci. doi: 10.1073/pnas.1710311114 (2017); Eurekalert press release