Dysfunctional Characteristics of Circulating Angiogenic Cells in Alzheimers Disease

Abstract

Vascular senescence contributes to the progression of Alzheimer's disease (AD) and circulating angiogenic cells (CACs) participate in the maintenance of the endothelium. As a step toward the development endothelial regeneration therapies for AD, we investigated the functional characteristics of CACs in AD patients. We enrolled AD patients and non-demented risk factor control subjects after matching for age, sex, and Framingham risk score. CACs were cultured from peripheral blood samples taken from subjects and used for various ex vivo assays. CACs from AD patients showed reduced chemotaxis, increased senescence, reduced paracrine angiogenic activity, and altered gene expression patterns compared to CACs from risk factor (RF) controls. Addition of high concentration A beta(1-42) (200, 2000 ng/mL) to the CAC culture reduced CAC counts and endothelial nitric oxide synthase/Akt phosphorylation and induced apoptosis. However, lower concentration of A beta(1-42) (2, 20 ng/mL) failed to reduce the CAC counts. CACs from AD patients were more susceptible to the cytotoxic effect of A beta(1-42) than CACs from RF controls. In summary, AD patients have intrinsic dysfunctions of CACs which provides an extended understanding of vascular endothelial pathogenesis in AD.