Dysfunctional Characteristics of Circulating Angiogenic Cells in Alzheimers Disease

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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.
Publisher
IOS PRESS
Issue Date
2010
Language
English
Article Type
Article
Keywords

ENDOTHELIAL PROGENITOR CELLS; BLOOD-BRAIN-BARRIER; COLONY-STIMULATING FACTOR; CORONARY-ARTERY-DISEASE; AMYLOID BETA-PEPTIDE; HEART-DISEASE; PLASMA-LEVELS; RISK-FACTORS; IMPAIRMENT; TRANSPORT

Citation

JOURNAL OF ALZHEIMERS DISEASE, v.19, no.4, pp.1231 - 1240

ISSN
1387-2877
DOI
10.3233/JAD-2010-1315
URI
http://hdl.handle.net/10203/98604
Appears in Collection
BiS-Journal Papers(저널논문)
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