There is strong evidence that inflammation occurs in different stages of Alzheimer’s disease (AD), and understanding this process can help us to design new therapeutic approaches. TREM2 is a protein that is directly related to the inflammation process that occurs in the brain of patients with AD; mutations in this protein increase the risk to develop AD up to threefold. A fragment of this protein, namely soluble TREM2 (sTREM2), can be detected in biological fluids like the cerebrospinal fluid (CSF). The function of sTREM2 in health and disease currently is not known. Our aim is to investigate the function of sTREM2 and any mutation-specific effect on its function by the use of novel mouse models. Importantly, we will establish the temporal expression of sTREM2 in the CSF of patients with or without familial history of the disease. By doing so we may provide evidence for a novel biomarker for neuronal cell death.