MAPT and Alzheimer disease: Because astrocytosis (i) is prominent around blood vessels in Alzheimer’s disease45; (ii) induced cerebral hypoperfusion, a characteristic of Down syndrome46; increases the number of GFAP-positive astrocytes47; and (iii) is an early disease feature of Alzheimer’s disease,48 we used a series of mediation and path analyses applied to cross-sectional data to test our hypothesis that cerebrovascular disease gives rise to tau pathology and ultimately neurodegeneration via astrocytosis across different Alzheimer’s disease stages in adults with Down syndrome.