Kapaki Elisabeth, Paraskevas George P, Papageorgiou Sokratis G, Bonakis Anastasios, Kalfakis Nikolaos, Zalonis Ioannis, Vassilopoulos Demetris
Department of Neurology, School of Medicine, Athens National University, Eginition Hospital, Athens, Greece.
Alzheimer Dis Assoc Disord. 2008 Jan-Mar;22(1):47-53. doi: 10.1097/WAD.0b013e3181610fea.
Cerebrospinal fluid (CSF) biomarkers have been increasingly studied in dementia clinical and differential diagnosis.
We assessed levels of total tau protein (tauT), tau phosphorylated at threonine 181 (tau P-181), and beta-amyloid1-42 (A beta 42) in 34 patients with frontotemporal lobar degeneration (FTLD), 76 Alzheimer disease (AD) cases, and 93 controls (CTRL). Double sandwich enzyme-linked immunosorbent assays (Innogenetics) were used for measurements.
Total tau was significantly increased and A beta 42 decreased in FTLD and AD patients as compared with CTRL. CSF tau P-181 levels were significantly increased only in AD. The tauT/A beta 42 ratio successfully discriminated FTLD from CTRL with a 86.7% specificity and 80.6% sensitivity, whereas the tauT alone was more specific (95.7%) but less sensitive (64.75%). For the discrimination of FTLD from AD, tauT/A beta 42 ratio was better (90.3% sensitivity and 64.5% specificity) compared with the other biomarkers alone or in combination, whereas tau P-181 was less sensitive but more specific (68.4% and 85.7%, respectively). Subtype analysis revealed that the most AD-like profile of biomarkers were observed in FTLD with motor neuron signs, whereas the most non-AD profile were observed in patients with primary progressive aphasia.
Combined analysis of CSF biomarkers may be useful for the best possible antemortem discrimination of FTLD from AD.
脑脊液（CSF）生物标志物在痴呆的临床和鉴别诊断中得到了越来越多的研究。
我们评估了34例额颞叶变性（FTLD）患者、76例阿尔茨海默病（AD）患者和93例对照者（CTRL）的总tau蛋白（tauT）、苏氨酸181位点磷酸化的tau蛋白（tau P-181）和β-淀粉样蛋白1-42（Aβ42）水平。采用双夹心酶联免疫吸附测定法（Innogenetics）进行检测。
与CTRL相比，FTLD和AD患者的总tau蛋白显著升高，Aβ42降低。仅在AD患者中，脑脊液tau P-181水平显著升高。tauT/Aβ42比值成功地将FTLD与CTRL区分开来，特异性为86.7%，敏感性为80.6%，而单独的tauT更具特异性（95.7%），但敏感性较低（64.75%）。对于区分FTLD与AD，tauT/Aβ42比值比单独或联合使用其他生物标志物更好（敏感性为90.3%，特异性为64.5%），而tau P-181敏感性较低但特异性较高（分别为68.4%和85.7%）。亚型分析显示，在伴有运动神经元体征的FTLD患者中观察到最类似AD的生物标志物特征，而在原发性进行性失语患者中观察到最不像AD的特征。
脑脊液生物标志物的联合分析可能有助于在生前最好地鉴别FTLD与AD。
