title: Interaction between cerebrovascular disease and Alzheimer pathology.
abstract: OBJECTIVE
  Epidemiological 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 Alzheimer's disease. In light of recent advances in basic, translational, and clinical research in the area, this review focuses on the significance of CVD in Alzheimer's disease pathogenesis.
  
  
  RESULTS
  Alzheimer's 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 Alzheimer's disease. Recent translational researches in this field aim to facilitate Aβ clearance. Several candidate drugs are being tested in clinical trials.
  
  
  CONCLUSIONS
  Compared 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 Alzheimer's disease and CVD suggests the necessity of the maintenance of cerebrovascular integrity, which may herald a new generation of dementia treatment strategies.
authors.affiliation: aDepartment of Regenerative Medicine and Tissue Engineering bDepartment of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000378:metabolism / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D003704:Dementia / Q000503:physiopathology; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006801:Humans; D008822:Mice, Transgenic; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced