Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56125, Pisa, Italy.
Alzheimers Res Ther. 2020 Nov 12;12(1):147. doi: 10.1186/s13195-020-00704-4.
Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development.
Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study).
We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score.
We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.
血浆神经丝轻链（NFL）和总 Tau（t-Tau）蛋白是阿尔茨海默病（AD）早期的候选生物标志物。生物因素对有主观记忆主诉（SMC）的个体血浆浓度的影响尚未得到充分研究。我们纵向研究了性别、年龄、APOE ε4 等位基因、合并症、脑β淀粉样蛋白（Aβ）负担和认知评分对认知健康个体 SMC 中血浆 NFL 和 t-Tau 浓度的影响，SMC 与 AD 发展相关。
分别有 316 名和 79 名个体进行了基线和三次时间点（基线、1 年和 3 年随访）的这两种生物标志物评估。在单中心队列（INSIGHT-preAD 研究）中使用超敏测定法测量了血浆生物标志物。
我们显示了年龄对血浆 NFL 的影响，随着时间的推移，女性血浆 t-Tau 浓度的增加高于男性。APOE ε4 等位基因不影响生物标志物浓度，而血浆维生素 B12 缺乏与较高的血浆 t-Tau 浓度相关。两种生物标志物均相关且随时间增加。基线 NFL 与 2 年随访时左后扣带回和下顶叶的 Aβ 沉积率相关。基线血浆 NFL 和血浆 t-Tau 变化率与认知评分呈负相关。
我们发现，在 SMC 个体中，血浆 NFL 和 t-Tau 的纵向轨迹分别受年龄和女性性别影响。探索生物变量对 AD 生物标志物的影响对于它们在血液中的临床验证至关重要。
