CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline

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.