Affiliations: [a] Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea | [b] Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea | [c] Brain Korea 21 Project for Medical Sciences, Seoul National University, Seoul, South Korea
Correspondence:
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Correspondence to: Jae-Kyu Roh, MD, PhD, Department of Neurology, Seoul National University Hospital, 101, Daehangno, Jongno-Gu, Seoul, 110-744, South Korea. Tel.: +82 2 2072 3265; Fax: +82 2 3672 4949; E-mail: rohjk@snu.ac.kr.
Note: [1] These authors contributed equally to this work.
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 Aβ1–42 (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 Aβ1–42 (2, 20 ng/mL) failed to reduce the CAC counts. CACs from AD patients were more susceptible to the cytotoxic effect of Aβ1–42 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.
