The Alzheimer's Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar

J Am Coll Cardiol. 2020 Mar 3;75(8):952-967. doi: 10.1016/j.jacc.2019.12.033.

Abstract

Aging-related cellular and molecular processes including low-grade inflammation are major players in the pathogenesis of cardiovascular disease (CVD) and Alzheimer's disease (AD). Epidemiological studies report an independent interaction between the development of dementia and the incidence of CVD in several populations, suggesting the presence of overlapping molecular mechanisms. Accumulating experimental and clinical evidence suggests that amyloid-beta (Aβ) peptides may function as a link among aging, CVD, and AD. Aging-related vascular and cardiac deposition of Αβ induces tissue inflammation and organ dysfunction, both important components of the Alzheimer's disease amyloid hypothesis. In this review, the authors describe the determinants of Aβ metabolism, summarize the effects of Aβ on atherothrombosis and cardiac dysfunction, discuss the clinical value of Αβ1-40 in CVD prognosis and patient risk stratification, and present the therapeutic interventions that may alter Aβ metabolism in humans.

Keywords: Alzheimer’s disease; amyloid precursor protein; amyloid-beta; atherosclerosis; cardiovascular disease; cardiovascular therapy; cerebral amyloid angiopathy; coronary artery disease; endothelial cells; leukocytes; platelets; prognosis; vascular dementia; vascular stiffness.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / physiology*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / prevention & control
  • Humans
  • Mortality
  • Risk Assessment

Substances

  • Amyloid beta-Peptides