比较血浆神经丝轻链和总 tau 作为神经退行性变标志物：与认知和神经影像学结果的关联。
Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes.
机构信息
Medical Scientist Training Program, Mayo Clinic Alix School of Medicine, Rochester, MN, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
出版信息
Alzheimers Res Ther. 2021 Dec 14;13(1):199. doi: 10.1186/s13195-021-00944-y.
BACKGROUND
Total tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma biomarkers of neurodegeneration, but studies have not compared how these biomarkers cross-sectionally or longitudinally associate with cognitive and neuroimaging measures. We therefore compared plasma T-Tau and NfL as cross-sectional and longitudinal markers of (1) global and domain-specific cognitive decline and (2) neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and white matter hyperintensity volume.
METHODS
We included 995 participants without dementia who were enrolled in the Mayo Clinic Study of Aging cohort. All had concurrent plasma NfL and T-tau, cognitive status, and neuroimaging data. Follow-up was repeated approximately every 15 months for a median of 6.2 years. Plasma NfL and T-tau were measured on the Simoa-HD1 Platform. Linear mixed effects models adjusted for age, sex, and education examined associations between baseline z-scored plasma NfL or T-tau and cognitive or neuroimaging outcomes. Analyses were replicated in Alzheimer's Disease Neuroimaging Initiative (ADNI) among 387 participants without dementia followed for a median of 3.0 years.
RESULTS
At baseline, plasma NfL was more strongly associated with all cognitive and neuroimaging outcomes. The combination of having both elevated NfL and T-tau at baseline, compared to elevated levels of either alone, was more strongly associated at cross-section with worse global cognition and memory, and with neuroimaging measures including temporal cortex thickness and increased number of infarcts. In longitudinal analyses, baseline plasma T-tau did not add to the prognostic value of baseline plasma NfL. Results using ADNI data were similar.
CONCLUSIONS
Our results indicate plasma NfL had better utility as a prognostic marker of cognitive decline and neuroimaging changes. Plasma T-tau added cross-sectional value to NfL in specific contexts.
TRIAL REGISTRATION
Not applicable.
背景
总 tau 蛋白（T-Tau）和神经丝轻链（NfL）已成为神经退行性变的候选血浆生物标志物，但这些研究尚未比较这些生物标志物如何与认知和神经影像学测量进行横截面或纵向关联。因此，我们比较了血浆 T-Tau 和 NfL 作为（1）整体和特定领域认知下降以及（2）皮质厚度、海马体积、白质完整性和白质高信号体积的神经影像学标志物的横截面和纵向标志物。
方法
我们纳入了 995 名无痴呆的梅奥诊所老龄化研究队列参与者。所有人均具有同时进行的血浆 NfL 和 T- tau、认知状态和神经影像学数据。随访大约每 15 个月重复一次，中位数为 6.2 年。在 Simoa-HD1 平台上测量血浆 NfL 和 T-Tau。线性混合效应模型调整了年龄、性别和教育，以研究基线 z 评分血浆 NfL 或 T-Tau 与认知或神经影像学结果之间的关联。在阿尔茨海默病神经影像学倡议（ADNI）中，在无痴呆的 387 名参与者中进行了复制，中位数随访时间为 3.0 年。
结果
在基线时，血浆 NfL 与所有认知和神经影像学结果的相关性更强。与单独升高 NfL 相比，基线时同时升高 NfL 和 T-Tau 与更差的整体认知和记忆以及包括颞叶皮质厚度和梗死数量增加在内的神经影像学测量结果的相关性更强。在纵向分析中，基线血浆 T-Tau 并未增加基线血浆 NfL 的预后价值。使用 ADNI 数据的结果相似。
结论
我们的结果表明，血浆 NfL 作为认知下降和神经影像学变化的预后标志物具有更好的应用价值。在特定情况下，血浆 T-Tau 增加了 NfL 的横截面价值。
试验注册
不适用。
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