MAPT and Alzheimer disease: Mounting vascular impairments occur in AD, including cerebral amyloid angiopathy, vessel tortuosity and rigidity, reduction in cerebral blood flow, and enlargement of periarterial and perivenous spaces; all of which impair glymphatic clearance, and are further impaired by the failure of glymphatic clearance with an abundance of Aβ and tau [226, 227] (Fig. 3a).