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阿尔茨海默病患者中伴有中度至重度痴呆的循环祖细胞增加:血管修复和组织再生的证据?

Increased circulating progenitor cells in Alzheimer's disease patients with moderate to severe dementia: evidence for vascular repair and tissue regeneration?

机构信息

Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls Universität Tübingen, Tübingen, Germany.

出版信息

J Alzheimers Dis. 2010;19(2):591-600. doi: 10.3233/JAD-2010-1261.

DOI:10.3233/JAD-2010-1261
PMID:20110604
Abstract

Cerebrovascular dysfunction is a common finding in patients with Alzheimer's disease (AD) and may contribute to cognitive decline. Abundant evidence suggests that vascular and neuronal repair mechanisms are mediated by circulating progenitor cells in vivo. Whether CD34+ and, specifically, CD34+/CD133+ progenitor cells are involved in the pathophysiology of AD is poorly understood so far. In the present study, peripheral blood concentrations of circulating CD34+/CD133+ and CD34+ progenitor cells were measured in 45 AD patients and in 30 healthy elderly controls by flow cytometry. The severity of dementia was assessed by Mini-Mental Status Examination and Clinical Dementia Rating scale. AD patients were stratified into two groups showing mild (n=17) and moderate to severe (n= 28) dementia. In the present study, AD patients with moderate to severe dementia, but not those with mild dementia, showed significantly increased circulating CD34+/CD133+ and CD34+ progenitor cells compared to healthy elderly controls independent of cardiovascular risk factors and medication. In addition, the number of circulating CD34+/CD133+ progenitor cells in AD patients was significantly inversely correlated with cognitive function, age, and plasma levels of SDF-1, the most potent chemokine for progenitor cells. Our findings suggest a stage-dependent upregulation of circulating CD34+/CD133+ and CD34+ progenitor cells in AD patients, which could take part in tissue healing processes of the brain in AD.

摘要

脑血管功能障碍是阿尔茨海默病(AD)患者的常见表现,并可能导致认知能力下降。大量证据表明,血管和神经元修复机制是由体内循环祖细胞介导的。目前为止,关于 CD34+祖细胞,特别是 CD34+/CD133+祖细胞是否参与 AD 的病理生理学过程还知之甚少。在本研究中,通过流式细胞术测量了 45 名 AD 患者和 30 名健康老年对照组的外周血循环 CD34+/CD133+和 CD34+祖细胞浓度。采用简易精神状态检查和临床痴呆评定量表评估痴呆的严重程度。将 AD 患者分为两组:轻度(n=17)和中重度(n=28)痴呆。本研究显示,中重度痴呆的 AD 患者,而不是轻度痴呆的患者,与健康老年对照组相比,循环 CD34+/CD133+和 CD34+祖细胞显著增加,与心血管危险因素和药物无关。此外,AD 患者循环 CD34+/CD133+祖细胞的数量与认知功能、年龄和 SDF-1(祖细胞最有效的趋化因子)的血浆水平呈显著负相关。我们的研究结果表明,AD 患者的循环 CD34+/CD133+和 CD34+祖细胞呈阶段性上调,可能参与 AD 患者大脑的组织修复过程。

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