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Authors: Rhodin, Johannes A. | Thomas, Tom N. | Clark, Linda | Garces, Amanda | Bryant, Margaret

Article Type: Research Article

Abstract: Vascular dysfunction and inflammatory processes may be early events in the pathology of Alzheimer's disease (AD). Even though amyloid β-peptides (Aβ) play a prominent role in the initiation and progression of cellular dysfunction in AD, the precise in vivo actions of various Aβ-peptides has not been established. The cerebrovascular actions of the major Aβ-peptides (1–40) and (1–42) in live animals were investigated using an open cranial window technique. We show here that the Aβ-peptides cause vascular lesions, especially in the arterioles. In one set of experiments, leukocytes and platelets were tagged with Rhodamine 6G, soluble Aβ(1–40) infused intravenously for 2 …minutes, and the vasculature video recorded for 90 minutes. In a second set of experiments, soluble Aβ(1–40) infusion was followed 30 minutes later by an infusion of soluble Aβ(1–42) and the vasculature recorded for 90 minutes. Fluorescent and transmission electron microscopic examinations demonstrated the following cerebrovascular action of Aβ-peptides: endothelial cell damage, leukocyte adhesion, platelet activation, thrombus formation, impeded blood flow, and smooth muscle cell damage. The vascular disruption observed were similar to those observed in the brains of some AD patients and may represent the initial phase of a vascular inflammatory response associated with cerebral amyloid angiopathy. The combination of Aβ(1–40) and (1–42) produced significantly more vascular disruption than Aβ(1–40) alone. Oral administration of conjugated estrogens in ovariectomized female rats protected them from the deleterious actions of Aβ-peptides. The reported protective effect of estrogen against AD may be mediated in part through prevention of cerebrovascular Aβ toxicity. Show more

Keywords: Alzheimer's disease, amyloid β-proteins, inflammation, leukocyte-platelet-endothelial interaction, thrombosis, conjugated estrogens, cranial window technique

DOI: 10.3233/JAD-2003-5403

Citation: Journal of Alzheimer's Disease, vol. 5, no. 4, pp. 275-286, 2003