We studied two independent cohorts from the University of California San Francisco (UCSF) and 1Florida Alzheimer's Disease Research Centers (1FLADRC) across the AD and cognitive continuum to investigate the effects of astrocyte reactivity (plasma GFAP) on different components of the AD cascade, including Aβ pathology (Aβ‐PET), phosphorylated and secreted AD tau (plasma phosphorylated tau [p‐tau]181 and p‐tau217), neurodegeneration (brain MRI, plasma neurofilament light [NfL]), and cognition (memory, executive functioning). Here, GFAP is linked to early-onset autosomal dominant Alzheimer disease.