Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether expression is changed in a disease severity-specific manner in . We measured in cerebrospinal fluid (CSF) in two of the best-characterized patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of causing dominant mutations, cross-sectionally assessed increased over the course of the disease and significantly differed from non-carriers 10 years before the expected symptom onset. In late-onset , higher was associated with more advanced disease stages and cognitive impairment. Higher was associated with higher soluble 2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although is not a diagnostic biomarker for , it may together with 2 reflect microglial activation during the disease.