<p>by Thomas S. Lewis, Jessica Wagner, Jonas J. Neher</p> Molecular profiling studies have mapped vascular alterations in Alzheimer’s disease, but have not proven a role for them in pathology. Longitudinal studies are needed to link molecular and structural changes to vascular mechanics, hemodynamics, and tissue perfusion. Molecular profiling studies have mapped vascular alterations in Alzheimer’s disease, but have not proven a role for them in pathology. This Perspective argues for longitudinal studies to link molecular and structural changes to vascular mechanics, hemodynamics and tissue perfusion.