Amyloid-β: A potential mediator of aging-related vascular pathologies

Abstract

Aging is one of the most promising risk factors for vascular diseases, however, the precise mechanisms mediating aging-related pathologies are not fully understood. Amyloid beta (Aβ), a peptide produced by the proteolytic processing of amyloid precursor protein (APP), is known as a key mediator of brain damage involved in the pathogenesis of Alzheimer's disease (AD). Recently, it was found that the accumulation of Aβ in the vascular wall is linked to a range of aging-related vascular pathologies, indicating a potential role of Aβ in the pathogenesis of aging-associated vascular diseases. In the present review, we have updated the molecular regulation of Aβ in vascular cells and tissues, summarized the relevance of the Aβ deposition with vascular aging and diseases, and the role of Aβ dysregulation in aging-associated vascular pathologies, including the impaired vascular response, endothelial dysfunction, oxidative stress, and inflammation. This review will provide advanced information in understanding aging-related vascular pathologies and a new avenue to explore therapeutic targets.

Keywords: Aging; Aβ; Hypertension; Inflammation; Oxidative stress; Vascular damage.

Fig. 1.

Vascular changes associated with Aβ deposition; Possible fates include ROS generation, impaired vascular response to stimuli, inflammation, atherosclerosis, vascular aging.

Fig. 2

Aβ induced ROS generation and associated events in vascular aging including endothelial dysfunction, increased cholesterol, stroke, vascular dementia, decreased NO production and atherosclerosis.