Cerebrospinal fluid total-tau (t-tau) and neurofilament light chain (NfL) are biomarkers of neurodegeneration and are increased in Alzheimer’s disease (AD). In order to adjust for age-related increases in t-tau and NfL, cross-sectional age-adjusted norms were developed based on amyloid negative cognitively normal (CN) adults aged 41–78 years (CN, n = 137). The age-adjusted norms for t-tau and NfL did not improve receiver operating curve based diagnostic accuracies in individuals with mild cognitive impairment (MCI) due to AD (AD-MCI, n = 144). Furthermore, while NfL was correlated with higher age in AD-MCI, no significant correlation was found for t-tau. The cox proportional hazard models, applied in 429 participants with baseline t-tau and NfL, showed higher hazard ratio of progression to MCI or dementia without age-adjustments (HR = 3.39 for t-tau and HR = 3.17 for NfL), as compared to using our norms (HR = 2.29 for t-tau and HR = 1.89 for NfL). Our results indicate that utilizing normative reference data could obscure significant age-related increases in these markers associated with neurodegeneration and AD leading to a potential loss of overall diagnostic accuracy.

中文翻译：

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年龄调整的 CSF t-tau 和 NfL 不会提高前驱阿尔茨海默病的诊断准确性


脑脊液总 tau (t-tau) 和神经丝轻链 (NfL) 是神经退行性变的生物标志物，在阿尔茨海默病 (AD) 中含量增加。为了调整 t-tau 和 NfL 与年龄相关的增加，根据 41-78 岁的淀粉样蛋白阴性认知正常 (CN) 成年人（CN，n = 137）制定了横断面年龄调整标准。 t-tau 和 NfL 的年龄调整标准并未提高 AD 引起的轻度认知障碍 (MCI) 个体基于受试者工作曲线的诊断准确性（AD-MCI，n = 144）。此外，虽然 NfL 与 AD-MCI 中的较高年龄相关，但 t-tau 未发现显着相关性。相比之下，在 429 名具有基线 t-tau 和 NfL 的参与者中应用的 cox 比例风险模型显示，在不进行年龄调整的情况下，进展为 MCI 或痴呆的风险比更高（t-tau 的 HR = 3.39，NfL 的 HR = 3.17）。使用我们的标准（t-tau 的 HR = 2.29，NfL 的 HR = 1.89）。我们的结果表明，利用规范参考数据可能会掩盖这些与神经退行性变和 AD 相关的标记物与年龄相关的显着增加，从而导致整体诊断准确性的潜在损失。