Studies in animal models have suggested that TREM2 is protective against Alzheimer’s disease (AD) pathology. Additionally, recent data has shown that longitudinal changes in soluble TREM2 levels in the cerebrospinal fluid (CSF) are associated with amyloid β (Aβ) deposition, tau-related pathology, and cognitive decline in autosomal dominant AD. Estrella Morenas-Rodriguez, MD, PhD, German Center for Neurodegenerative Diseases, Munich, Germany, comments on efforts to boost TREM-2 therapeutically in order to slow the progression of AD. Preclinically, several groups are working to enhance TREM2 activity using antibodies that stabilize TREM2 on the cell surface and reduce its proteolytic shedding. In mouse models of AD pathology, TREM2 antibodies have been shown to enhance microglial TREM2 expression and reduce amyloid plaque pathology. Promising data suggesting target engagement and safety have also been published from a first-in-human single ascending dose study in healthy volunteers (NCT03635047). This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.