MAPT and amyloidosis: This multicenter study has 3 main findings: first, we demonstrate the influence of VRFs and cSVD on CSF Aβ1-42 levels; second, we found an indirect association of VRFs with amyloid pathology through the presence of cSVD; and third, we showed that cSVD is indirectly associated with tau accumulation, gray matter atrophy (also over time), and cognitive impairment through amyloid pathology.