Interaction between cerebrovascular disease and Alzheimer pathology

PURPOSE OF REVIEWEpidemiological investigations have proposed strict control of vascular risk factors as a strategy to overcome dementia, because of the close interaction between cerebrovascular disease (CVD) and Alzheimerʼs disease. In light of recent advances in basic, translational, and clinical research in the area, this review focuses on the significance of CVD in Alzheimerʼs disease pathogenesis. RECENT FINDINGSAlzheimerʼs disease and CVD share several risk factors, and the coexistence of both pathologies is frequently noted. CVD and subsequent cerebral blood flow reduction would increase amyloid β (Aβ) production by modulating β and γ-secretase. Furthermore, CVD impairs Aβ clearance, which is mainly driven by vascular mediated systems, including active transport across the blood–brain barrier, and perivascular lymphatic/paravascular glymphatic drainage systems. Thus, CVD may disturb homeostasis between Aβ production and clearance, thereby aggravating Alzheimerʼs disease. Recent translational researches in this field aim to facilitate Aβ clearance. Several candidate drugs are being tested in clinical trials. SUMMARYCompared with Aβ pathology, little is known about the relationship between tau pathology and CVD, although some studies have shown that CVD has an influence on tau pathology. The close interrelationship between Alzheimerʼs disease and CVD suggests the necessity of the maintenance of cerebrovascular integrity, which may herald a new generation of dementia treatment strategies.