Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer’s disease (AD) pathology (amyloid-β [Aβ42/40], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Here, NEFL is linked to early-onset autosomal dominant Alzheimer disease.