Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University, Goettingen, Germany.
Department of Nuclear Medicine, University Medical Center Goettingen (UMG), Georg-August-University, Goettingen, Germany.
J Alzheimers Dis. 2018;62(1):203-212. doi: 10.3233/JAD-170793.
Analysis of cerebrospinal fluid (CSF) is one of the key tools for the state-of-the-art differential diagnosis of dementias. Dementia due to Alzheimer's disease (AD) is characterized by elevated CSF levels of total Tau (tTau) and phospho-181-Tau (pTau) and low CSF amyloid-β42 (Aβ42). Discrepancies in the laboratory analysis of human materials are well known and much effort has been put into harmonization procedures. In this study, we measured CSF biomarkers of more than 100 patients obtained under clinical routine conditions in two different clinical laboratories. The CSF biomarker levels obtained from the two different sites were significantly correlated: R2 = 0.7129 (tTau, p < 0.001), 0.7914 (pTau, p < 0.001), 0.5078 (Aβ42, p < 0.001), 0.5739 (Aβ40, p < 0.001), and 0.4308 (Aβ42/40, p < 0.001). However, the diagnostic classifications of the Aβ42, tTau, and pTau levels of identical subjects into normal versus pathological range made by the two different sites showed substantial discrepancies (31.5%, 29.6%, and 25.0% discordant cases, respectively). Applying Aβ42/40, instead of CSF Aβ42 alone, lead to a reduction of the discordant cases to 16.8%. Our findings suggest that CSF Aβ42/40 can outperform Aβ42 as a biomarker for AD neuropathology, not only under well-controlled study conditions but also in real life clinical routine. Thus, we recommend the inclusion of Aβ42/40 as a CSF biomarker in the diagnostic procedure.
分析脑脊液（CSF）是目前痴呆症鉴别诊断的重要工具之一。阿尔茨海默病（AD）引起的痴呆症的特点是脑脊液中总 Tau（tTau）和磷酸化 181-Tau（pTau）水平升高，而 CSF 中的淀粉样蛋白-β42（Aβ42）水平降低。众所周知，人体材料的实验室分析存在差异，人们为此付出了很大的努力来协调这些差异。在这项研究中，我们在两个不同的临床实验室中，对 100 多名患者的脑脊液生物标志物进行了测量。从两个不同地点获得的 CSF 生物标志物水平显著相关：R2=0.7129（tTau，p<0.001），0.7914（pTau，p<0.001），0.5078（Aβ42，p<0.001），0.5739（Aβ40，p<0.001）和 0.4308（Aβ42/40，p<0.001）。然而，对相同受试者的 CSF Aβ42、tTau 和 pTau 水平进行的正常与病理范围的诊断分类，由两个不同的实验室做出的结果显示出很大的差异（分别有 31.5%、29.6%和 25.0%的不一致病例）。应用 Aβ42/40，而不是单独的 CSF Aβ42，可将不一致病例减少到 16.8%。我们的研究结果表明，CSF Aβ42/40 作为 AD 神经病理学的生物标志物，不仅在严格控制的研究条件下，而且在现实生活的临床常规中，都可以优于 Aβ42。因此，我们建议将 Aβ42/40 纳入 CSF 生物标志物的诊断程序中。
