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ARTICLES: S-T Lee, K. Chu, K-H Jung, H-K Park, D-H Kim, J-J Bahn, J-H Kim, M-J Oh, S. K. Lee, M. Kim, and J-K Roh Reduced circulating angiogenic cells in Alzheimer disease Neurology 2009; 72: 1858-1863 [Abstract] [Full text] [PDF]

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Reduced circulating angiogenic cells in Alzheimer disease

Steven R. Brenner, None   (17 August 2009)

Reply from the authors

Jae-Kyu Roh, Soon-Tae Lee, Kon Chu, Keun-Hwa Jung, Sang Kun Lee, Manho Kim   (17 August 2009)

Reduced circulating angiogenic cells in Alzheimer disease 17 August 2009
Steven R. Brenner, Dept. Neurology at St. Louis VA Med Ctr & Dept. Neurology and Psychiatry at St. Louis University 915 North Grand. St. Louis, MO 63106, None Send Correspondence to journal: Re: Reduced circulating angiogenic cells in Alzheimer disease SBren20979{at}aol.com Steven R. Brenner, et al.	I read the article by Lee et al. who reported decreased numbers of circulating angiogenic cells in Alzheimer disease (AD). [1] This may be associated with impairment of the blood brain barrier (BBB) permitting toxic substances such as beta amyloid to penetrate the brain. Brain endothelial cells regulate AD amyloid (Abeta) levels in the neuronal microenvironment. Conversely, Abeta is toxic to neuroendothelial cells, which reduces their survival, yet Abeta(1-42) complexed with Al(3+) or Abeta(1-42)-Al increases the toxicity of neuroendothelial cells. [2] Patients with AD have significantly higher levels of serum aluminum (AL) than patients with other forms of dementia and age matched controls. [3] Vascular endothelial growth factor (VEGF) phenotypes may also contribute to development of AD. This is because the AA phenotype is associated with an increased risk of developing AD and accelerated cognitive decline in ApoE 4 positive patients. [4] VEGF variation may lead to decreased stimulation of angiogenic cells. The brain endothelial cell may play a major role in the development of AD through secretion of amyloid beta precursor and neurotoxic peptide. [5] Failure of the neuroendothelium BBB—through impaired angiogenesis from an interplay of toxic and endogenous factors—may lead to leakage of beta amyloid precursors and toxic neuropeptides into the brain parenchyma with subsequent development of AD. Measures to restore angiogenesis and the BBB may have the potential to prevent and treat AD. References 1. Lee S-T, Chu K, Jung K-H, et al. Reduced circulating angiogenic cells in Alzheimer disease. Neurology 2009;72:1858-1863. 2. Drago D, Folin M, Baiguera S, Tognon G, Ricchelli F, Zatta P. Comparative effects of Abeta(1-42)-Al from rat and human amyloid on rat endothelial cell cultures. J of Alzheimers Dis 2007;11:33-44. 3. Zapatero MD, Garcia de Jalon A, Pascual F, Calvo ML, Escareno J, Marro A. Serum aluminum levels in Alzheimer disease and other senile dementias. Biol Trace Elem Res 1995;47:235-240. 4. Chiappelli M, Borroni B, Archetti S, et al. VEGF gene and phenotype relation with Alzheimer disease and Mild cognitive impairment. Rejunvenation Res 2006;9:485-493. 5. Vagnucci AH, Li WW. Alzheimer’s disease and angiogenesis. Lancet 2003;361:605-608. Disclosure: Dr. Brenner reports no disclosures.
Reply from the authors 17 August 2009
Jae-Kyu Roh, Department of Neurology, Seoul National University Hospital 101, Daehangno, Jongno-Gu, Seoul 110-744, South Korea., Soon-Tae Lee, Kon Chu, Keun-Hwa Jung, Sang Kun Lee, Manho Kim Send Correspondence to journal: Re: Reply from the authors rohjk{at}snu.ac.kr Jae-Kyu Roh, et al.	We thank Dr. Brenner for his interest in our article. Abeta in the AD brain contributes to cerebral endothelial damage and aberrant angiogenesis, [5,6] which can cause consumptive loss of circulating angiogenic cells. Another report suggests the possibility of impaired mobilization of bone marrow-derived circulating progenitor cells in AD. [7] Conversely, reduced circulating angiogenic cells in AD are short for maintenance of degenerating BBB, [8] which can accelerate impaired Abeta homeostasis. There is a relationship among circulating angiogenic cells, cerebral endothelial cells, the BBB, and Abeta homeostasis. These associations may hold promise for the further understanding of AD pathogenesis and lead to more effective AD treatment. References 6. Gentile MT, Vecchione C, Maffei A et al. Mechanisms of soluble beta-amyloid impairment of endothelial function. J Biol Chem 2004;279:48135-48142. 7. Laske C, Stellos K, Stransky E, Leyhe T, Gawaz M. Decreased Plasma Levels of Granulocyte-Colony Stimulating Factor (G-CSF) in Patients with Early Alzheimer's Disease. J Alzheimers Dis 2009;17:115-123. 8. Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004;95:343-353. Disclosure: Dr. Roh serves as Associate Editor of Laboratory Investigation. Drs. Lee, Chu, Jung, Lee, and Kim report no disclosures.