Merluzzi Andrew P, Vogt Nicholas M, Norton Derek, Jonaitis Erin, Clark Lindsay R, Carlsson Cynthia M, Johnson Sterling C, Asthana Sanjay, Blennow Kaj, Zetterberg Henrik, Bendlin Barbara B
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
Alzheimers Dement (N Y). 2019 Apr 12;5:129-138. doi: 10.1016/j.trci.2019.02.004. eCollection 2019.
Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t-tau and alternative biomarkers of neurodegeneration-neurogranin and neurofilament light protein (NFL)-add value in predicting subclinical cognitive decline.
One hundred fifty cognitively unimpaired participants received a lumbar puncture for cerebrospinal fluid and at least two neuropsychological examinations (mean age at first visit = 59.3 ± 6.3 years; 67% female). Linear mixed effects models were used with cognitive composite scores as outcomes. Neurodegeneration interactions terms were the primary predictors of interest: age × NFL or age × neurogranin or age × t-tau. Models were compared using likelihood ratio tests.
Age × NFL accounted for a significant amount of variation in longitudinal change on preclinical Alzheimer's cognitive composite scores, memory composite scores, and learning scores, whereas age × neurogranin and age × t-tau did not.
These data suggest that NFL may be more sensitive to subclinical cognitive decline compared to other proposed biomarkers for neurodegeneration.
神经退行性变似乎是阿尔茨海默病认知衰退最直接的生物学机制。我们测试了总tau蛋白（t-tau）以及神经退行性变的替代生物标志物——神经颗粒素和神经丝轻链蛋白（NFL）在预测亚临床认知衰退方面是否具有额外价值。
150名认知功能未受损的参与者接受了腰椎穿刺以获取脑脊液，并至少接受了两次神经心理学检查（首次就诊时的平均年龄 = 59.3 ± 6.3岁；67%为女性）。以认知综合评分作为结果，使用线性混合效应模型。神经退行性变交互项是主要的研究预测因素：年龄×NFL或年龄×神经颗粒素或年龄×t-tau。使用似然比检验对模型进行比较。
年龄×NFL在临床前阿尔茨海默病认知综合评分、记忆综合评分和学习评分的纵向变化中占显著比例的变异，而年龄×神经颗粒素和年龄×t-tau则不然。
这些数据表明，与其他提出的神经退行性变生物标志物相比，NFL可能对亚临床认知衰退更敏感。
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