Brettschneider J, Maier M, Arda S, Claus A, Süssmuth S D, Kassubek J, Tumani H
Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Mult Scler. 2005 Jun;11(3):261-5. doi: 10.1191/1352458505ms1159oa.
Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo. We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing-remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus 152.0 pg/mL; P = 0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P = 0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity.
轴突损伤被认为是多发性硬化症永久性临床残疾的主要基础。 Tau蛋白是一种定位于神经元轴突的微管相关蛋白,可作为一种生化替代标志物来评估体内的轴突损伤。我们旨在通过研究脑脊液tau浓度来确定不同阶段和临床亚型的多发性硬化症患者轴突损伤的程度。使用免疫测定法对35例复发缓解型多发性硬化症患者、8例继发进展型多发性硬化症患者、9例原发进展型多发性硬化症患者、50例提示早期多发性硬化症的临床孤立综合征患者和46例正常对照者进行tau检测。与正常对照相比,多发性硬化症患者脑脊液tau显著升高(中位数206.0 pg/mL对152.0 pg/mL;P = 0.002)。尽管在疾病的极早期阶段发现tau水平最高,但在不同亚型的多发性硬化症之间未检测到显著差异。磁共振成像中钆增强脑病变患者的脑脊液tau显著升高(P = 0.02),鞘内IgG合成明显的患者脑脊液tau水平有升高趋势,这支持了轴突损伤受炎症活动影响的观点。