Little is known about the role of microglia in Alzheimer’s disease (AD). TREM2 is a protein expressed by microglia. Mutations in TREM2 increase the risk for neurodegenerative diseases including AD. Suárez-Calvet and colleagues have measured the amount of a secreted form of TREM2 (sTREM2) as a surrogate marker for microglial activation. They measured sTREM2 in the cerebrospinal fluid (CSF) of a unique cohort of 127 subjects with autosomal dominant AD and 91 healthy siblings. CSF sTREM2 was abnormally increased 5 years before the expected onset of symptoms in the AD patients. This increase occurred after alterations in markers for brain amyloidosis and neuronal injury.