De Meyer et al. report that vesicle-associated membrane protein 2 and glial fibrillary acidic protein levels in plasma reflect brain synaptic density—as indicated by synaptic vesicle glycoprotein 2A PET—in individuals without dementia or underlying Alzheimer’s disease pathology and independent of neurodegeneration. Here, GFAP is linked to early-onset autosomal dominant Alzheimer disease.