title: Influence of Low-Dose Aspirin on Cerebral Amyloid Angiopathy in Mice.
abstract: Accumulation of amyloid-β peptide (Aβ) in the brain is one of the most important features of Alzheimer's dementia (AD). Cerebral amyloid angiopathy (CAA) is characterized by Aβ accumulation in the walls of cerebral arteries and capillaries, and is present in over 90% of patients with AD. Several novel agents for AD/CAA developed around the amyloid hypothesis have shown positive signs in animal studies but have failed in clinical trials due to adverse events and/or lack of efficiency. As CAA is presumably caused by a failure in Aβ clearance, drugs that promote Aβ clearance may hold promise in the treatment of CAA and possibly AD. With this in mind, cilostazol, an anti-platelet drug with vasodilating action, has been found to promote Aβ clearance along perivascular drainage pathway, reduce Aβ accumulation in the brain, and restore memory impairment in Tg-SwDI mice, an animal model of CAA. We therefore tested whether the most common anti-platelet agent, aspirin, also reduced Aβ and rescued cognitive impairment in Tg-SwDI mice, and also whether aspirin affected hemorrhagic complications that can occur in Tg-SwDI mice. Mice aged 4 months were assigned into vehicle-treated and low-dose aspirin-treated groups. Low-dose aspirin for 8 months did not increase hemorrhagic lesions, nor increase resting cerebral blood flow or cerebral vascular reserve in response to hypercapnia or acetylcholine. Subsequently, aspirin did not restore cognitive dysfunction. These results suggest that low-dose aspirin does not have a direct influence on cerebrovascular Aβ metabolism nor aggravate hemorrhagic complications in CAA.
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Yorito
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan.
authors.forename: Takakuni
authors.initials: T
authors.lastname: Maki
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan.|Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagatsuka
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.|Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016229:Amyloid beta-Peptides; D001241:Aspirin
keywords: Alzheimer’s dementia; amyloid β; aspirin; cerebral amyloid angiopathy