Elevated levels of TREM2 in monocytes linked to Alzheimer’s development

Written by Alice Weatherston

Researchers from Brigham and Women’s Hospital (MA, USA) have this week published a new study which may help to unravel the role of the immune system in Alzheimer’s disease. The team hope that the findings, which were published in Nature Neuroscience, could help to inform the development of future therapeutics and prediction strategies for the disease.
“There’s an emerging theme in Alzheimer’s genetics that the immune system may be strongly involved in the onset of Alzheimer’s disease,” commented Philip De Jager (Brigham and Women’s Hospital).

Under the lead of De Jager, the study group looked to investigate the link between genetic risk factors and their influence on monocytes. The team examined blood samples of 100 younger, healthy subjects as well as 61 older subjects and evaluated the levels of key proteins in the monocytes in relation to genetic variants that have previously been linked to Alzheimer’s disease.

The results indicated that higher levels of the protein termed TREM2, which is currently a major target of many Alzheimer’s drug development programmes, are associated with an increased risk of Alzheimer’s disease. Prior to this, despite identifying that a specific mutation in TREM2 results in an elevated Alzheimer’s risk, it was unclear as to whether it was higher or lower levels of TREM2 were responsible for this. The study therefore provides definitive evidence where other follow-up studies in mice have produced often conflicting results.

In addition to this, a genetic variant linked to a separate protein termed CD33 also had an effect on TREM2 levels, with the genetic variant resulting in more CD33 and in turn leading to increased levels of TREM2.

“One interesting note about these protein associations is that we did not observe them at the mRNA level,” added Gail Chan (Brigham and Women’s Hospital). “This emphasizes the amount of inter-regulation that a cell does to balance all of the related molecules in order to function correctly.”

Looking forward, the team plan to expand the study as part of the Brigham Healthy Aging Project, measuring CD33 and TREM2 levels in subjects to determine if the factors implicated in this study could be used within a diagnostic panel for predicting the risk of development of Alzheimer’s.

“Further studies are needed to understand the connections we’re uncovering and the roles of these proteins, but we’re clearly seeing evidence that these genetic variants have an effect in this type of immune cell,” concluded Elizabeth Bradshaw (Brigham and Women’s Hospital).

Source: Brigham and Women’s Hospital press release