On 28 August, Dr Michael Ewers and colleagues published a paper in Science Translational Medicine, showing that people with higher cerebrospinal fluid TREM2 levels experienced slower cognitive decline during the development of Alzheimer’s disease (AD). TREM2 is a protein that sits on the surface of microglia, specialised cells that orchestrate inflammatory responses in the brain. TREM2 is thought to regulate the behaviour of microglia, controlling whether they adopt pathological or beneficial characteristics. However, studies have yet to conclusively show whether TREM2 affects cognitive decline in people with AD.
To answer this question, researchers turned to the Alzheimer’s Disease Neuroimaging (ADNI) Initiative, a longitudinal multicentre study which collects and shares data from participants with pre-symptomatic and symptomatic AD. Since 2004, ADNI has collected annual brain scans, genetic profiles, blood and cerebrospinal fluid (CSF) samples from hundreds of participants with mild cognitive impairment (MCI), early AD or advanced AD, sharing them withbona fideresearchers upon request.
Using CSF samples from ADNI, Dr. Ewers and his two joint first authors, Dr. Franzmaier and Dr. Suarez-Calvet, assessed the levels of TREM2 in 385 participants. Aiming to understand whether baseline levels of TREM2 could predict cognitive decline during the development of symptomatic AD, they found that participants with higher baseline soluble TREM2 (sTREM2) showed a slower decline in cognitive test scores over time. When they looked at the levels of p-Tau, a well-known biomarker of AD, they observed that participants with a higher ratio of sTREM2 to p-Tau, showed a slower conversion from MCI to symptomatic AD. This was associated with a slower development of hippocampal shrinkage over time, measured by analysing the annual MRI scans collected from ADNI participants. Based on these findings, the researchers hypothesised that higher TREM2 may have a protective effect in the brain, suggesting that therapies which stimulate TREM2 activity may be beneficial for people in the early stages of AD.