Characteristics of thein VitroVasoactivity of β-Amyloid Peptides

Crawford, Fiona; Suo, Zhiming; Fang, Chuo; Mullan, Michael

doi:10.1006/exnr.1997.6743

Cited by 105 publications

(88 citation statements)

References 42 publications

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“…Taken together, however, the data demonstrate profound impairment of the functional integrity of cerebrovascular responses because of overexpression of mutant APP and A␤ deposition, and imply that functional alterations are also likely to occur in CAA and AD. These in vivo results, together with observations that A␤ has a positive ionotropic effect on aortic rings studied ex vivo, 19,20 support the hypothesis that vessel-associated A␤ causes a physiologically relevant impairment of cerebrovascular vessel structure and function.…”

Section: Discussionsupporting

confidence: 70%

Structural and Functional Disruption of Vascular Smooth Muscle Cells in a Transgenic Mouse Model of Amyloid Angiopathy

Christie

Yamada

Moskowitz

et al. 2001

The American Journal of Pathology

123

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The deposition of amyloid A␤ peptide in the wall of cerebral vessels (cerebral amyloid angiopathy), can lead to weakness and rupture of the vessel wall, resulting in hemorrhagic stroke. The Tg2576 transgenic mouse line, overexpressing mutant amyloid precursor protein in an age-dependent manner, forms amyloid angiopathy morphologically similar to that seen in the human. We report here the structural and functional disruption of smooth muscle cells (SMCs) in the walls of pial vessels affected by amyloid deposition in the Tg2576 mouse. We demonstrate, using multiphoton imaging, that the arrangement of SMCs becomes disorganized before the onset of cell death, and that these disorganized SMCs are unable to respond appropriately to application of endothelial-dependent and endothelial-independent vasodilators in a closedcranial window preparation.

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Section: Discussionsupporting

confidence: 70%

Structural and Functional Disruption of Vascular Smooth Muscle Cells in a Transgenic Mouse Model of Amyloid Angiopathy

Christie

Yamada

Moskowitz

et al. 2001

The American Journal of Pathology

123

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“…Importantly, this impairment of functional hyperemia appeared prior to the appearance of amyloid in plaques and the vasculature and regional CBF was reduced as a result of soluble amyloid on eliciting vasoconstriction and attenuating endotheliummediated vasodilation. Furthermore, superfusion of the neocortex with Aβ led to deficits in hyperemia in wild type mice and previous studies examining the effects of Aβ on isolated vessels add further support for the vascular effects of this peptide (Thomas et al, 1996;Crawford et al, 1998).…”

Section: Vasoactive Properties Of Aβsupporting

confidence: 53%

Linking vascular disorders and Alzheimer's disease: Potential involvement of BACE1

Cole¹,

Vassar²

2009

Neurobiology of Aging

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The etiology of Alzheimer's disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation.

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“…A␤-induced vascular inflammation, activation of scavenger receptors, and upregulation of endothelin-1 have all been implicated (Crawford et al, 1998;Deane et al, 2003;Paris et al, 2003). Central to these mechanisms is increased production of reactive oxygen species (ROS) leading to vascular oxidative stress Niwa et al, 2000bNiwa et al, , 2001bParis et al, 2003;Park et al, 2004a).…”

Section: Introductionmentioning

confidence: 99%

NADPH Oxidase-Derived Reactive Oxygen Species Mediate the Cerebrovascular Dysfunction Induced by the Amyloid β Peptide

Park¹,

Anrather²,

Zhou³

et al. 2005

J. Neurosci.

223

229

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Overproduction of the amyloid ␤ (A␤) peptide is a key factor in the pathogenesis of Alzheimer's disease (AD), but the mechanisms of its pathogenic effects have not been defined. Patients with AD have cerebrovascular alterations attributable to the deleterious effects of A␤ on cerebral blood vessels. We report here that NADPH oxidase, the major source of free radicals in blood vessels, is responsible for the cerebrovascular dysregulation induced by A␤. Thus, the free-radical production and the associated alterations in vasoregulation induced by A␤ are abrogated by the NADPH oxidase peptide inhibitor gp91ds-tat and are not observed in mice lacking the catalytic subunit of NADPH oxidase (gp91 phox ). Furthermore, oxidative stress and cerebrovascular dysfunction do not occur in transgenic mice overexpressing the amyloid precursor protein but lacking gp91 phox . The mechanisms by which NADPH oxidase-derived radicals mediate the cerebrovascular dysfunction involve reduced bioavailability of nitric oxide. Thus, a gp91 phox -containing NADPH oxidase is the critical link between A␤ and cerebrovascular dysfunction, which may underlie the alteration in cerebral blood flow regulation observed in AD patients.

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Characteristics of thein VitroVasoactivity of β-Amyloid Peptides

Cited by 105 publications

References 42 publications

Structural and Functional Disruption of Vascular Smooth Muscle Cells in a Transgenic Mouse Model of Amyloid Angiopathy

Structural and Functional Disruption of Vascular Smooth Muscle Cells in a Transgenic Mouse Model of Amyloid Angiopathy

Linking vascular disorders and Alzheimer's disease: Potential involvement of BACE1

NADPH Oxidase-Derived Reactive Oxygen Species Mediate the Cerebrovascular Dysfunction Induced by the Amyloid β Peptide

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