Measurement of thirteen biological markers in CSF of patients with Alzheimer's disease and other dementias

Measurement of thirteen biological markers in CSF of patients with Alzheimer's disease and other dementias
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DOI:
10.1159/000089137
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发表时间:
2006-01-01
影响因子:
2.4
通讯作者:
Humpel, C
Humpel, C
中科院分区:
医学4区
文献类型:
--
作者:
Blasko, I;Lederer, W;Humpel, C

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脑脊液(CSF)生物标志物对痴呆的诊断有一定价值。本研究的目的是评价阿尔茨海默病(AD)、额叶痴呆、酒精性痴呆、重度抑郁症患者和正常对照组脑脊液中13种可能的生物标志物的水平。这项研究以β-淀粉样蛋白1-42(Aβ42)、总tau和磷酸化tau-181(P-tau181)为核心标记物。P-tau181/Aβ42比值可显著区分AD患者和其他诊断亚组。5种生长因子(HGF、GDNF、血管内皮生长因子、BDNF、成纤维细胞生长因子-2)和3种细胞因子/趋化因子(肿瘤坏死因子-α、转化生长因子-β(1)、巨噬细胞趋化因子-1α)的水平在研究组之间差异无统计学意义。然而,根据神经变性的程度(由P-tau181/Aβ42表示),与健康对照组相比,AD患者脑脊液中神经生长因子(NGF)水平显著升高。脑脊液中单核细胞趋化蛋白-1(MCP-1)水平在所有组中均随年龄增长而显著升高,但不能区分AD患者和健康对照组。结果证实了P-tau181/Aβ42比值在AD诊断中的适用性,而脑脊液中NGF和MCP-1水平对AD的诊断特异性和可靠性较低。提示NGF的升高与AD神经退行性变的程度和MCP-1随年龄的增加有关。版权所有(C)2006 S.Karger AG,巴塞尔。
Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer's disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using beta-amyloid 1-42 (A beta 42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/A beta 42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-alpha, TGF-beta(1), MIP-1 alpha) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/A beta 42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/A beta 42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age. Copyright (C) 2006 S. Karger AG, Basel.