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NEUROLOGY 2009;72:1858-1863
© 2009 American Academy of Neurology

Reduced circulating angiogenic cells in Alzheimer disease

S-T Lee, MD, K. Chu, MD, PhD, K-H Jung, MD, H-K Park, MD, D-H Kim, MS, J-J Bahn, MS, J-H Kim, MS, M-J Oh, BS, S. K. Lee, MD, PhD, M. Kim, MD, PhD and J-K Roh, MD, PhD

From the Department of Neurology (S.-T.L., K.C., K.-H.J., H.-K.P., D.-H.K., J.-J.B., J.-H.K., M.-J.O., S.K.L., M.K., J.-K.R.), Clinical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., K.C., K.-H.J., H.-K.P., J.-J.B., S.K.L., M.K., J.K.R.), Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.

Address correspondence and reprint requests to Dr. Jae-Kyu Roh, Department of Neurology, Seoul National University Hospital, 101, Daehangno, Jongno-Gu, Seoul, 110-744, South Korea rohjk{at}snu.ac.kr

Objective: Neurovascular dysfunction and senescent endothelium contribute to the progression of Alzheimer disease (AD). Circulating angiogenic cells (CACs), such as endothelial progenitor cells (EPCs), provide a cellular reservoir for the endothelial replacement. To study the involvement of CACs in AD pathogenesis, we investigated the levels of CACs in patients with AD.

Methods: Consecutive patients with newly diagnosed AD (n = 55), patients with non-AD neurodegenerative diseases (n = 37), and nondemented risk factor control subjects (RF control, n = 55 and 37) were enrolled after matching for age, sex, and Framingham risk score. Peripheral blood samples were taken, and EPC colony-forming units (CFU-EPC) were cultured and counted.

Results: The patients with AD had significantly lower CFU-EPC than the RF controls. In the patients with AD, a lower CFU-EPC was independently associated with either a lower Mini-Mental State Examination score or a higher Clinical Dementia Rating scale score, indicating a greater reduction in CFU-EPC in advanced AD. Patients with non-AD neurodegenerative diseases did not show a significant decrease in CFU-EPC levels.

Conclusion: Our results indicate that patients with Alzheimer disease (AD) have reduced circulating angiogenic cells, suggesting that an abnormal capacity to regenerate endothelium is associated with AD.

Abbreviations: β = amyloid β peptide; AD = Alzheimer disease; ADAS-cog = cognitive subscale of Alzheimer's Disease Assessment Scale; ALS = amyotrophic lateral sclerosis; BBB = blood-brain barrier; CAC = circulating angiogenic cells; CDR = Clinical Dementia Rating scale; CFU = colony-forming units; EPC = endothelial progenitor cells; FRS = Framingham Risk Score; MMSE = Mini-Mental State Examination; NAND = non-AD neurodegenerative diseases; PBMC = peripheral blood mononuclear cell; PD = Parkinson disease; RF = risk factor.

Supplemental data at www.neurology.org

*These authors contributed equally.

Authors' full names are provided at the end of the article.

Supported by a grant (SC4120) from the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, a grant (A080448) from the Korea Healthcare technology R&D Project funded by Ministry of Health & Welfare, and a grant (year 2008, 800-20080511) from the Interdisciplinary Research Initiatives Program by College of Medicine, Seoul National University, South Korea.

Disclosure: The authors report no disclosures.

Medical Devices: 2% gelatin-coated 12-well plates and Histopaque 1077 (Sigma-Aldrich, St. Louis, MO); BulletKit (CC-3162; Clonetics, Walkersville, MD).

Received November 2, 2008. Accepted in final form February 27, 2009.




Correspondence:

Read all Correspondence

Reduced circulating angiogenic cells in Alzheimer disease
Steven R. Brenner, et al.
Neurology Online, 17 Aug 2009 [Full text]
Reply from the authors
Jae-Kyu Roh, et al.
Neurology Online, 17 Aug 2009 [Full text]

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