In the current study, we examined the association between WMH, as a marker of small vessel cerebrovascular disease, and Alzheimer’s disease plasma biomarker concentrations, including Aβ40/Aβ42, phosphorylated tau 217 (p-tau217) and GFAP, with neurofilament light chain (NfL) across disease stages in adults with Down syndrome. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.