Plasma biomarkers of dementia, including phosphorylated tau (p-tau217), offer promise as tools for diagnosis, stratification for clinical trials, monitoring disease progression, and assessing the success of interventions in those living with Alzheimer’s disease. However, currently, it is unknown whether these dementia biomarker levels vary with time of day, which could have implications for their clinical value. In two protocols, we studied 38 participants (70.8 ± 7.6 years; mean ± SD) in a 27-hour laboratory protocol with either two samples taken 12 hours apart or 3-hourly blood sampling for 24 hours in the presence of a sleep-wake cycle. The study population comprised people living with mild Alzheimer’s disease (PLWA, n = 8), partners/caregivers of PLWA (n = 6) and cognitively intact older adults (n = 24). Single molecule array technology was used to measure phosphorylated tau (p-tau217) (ALZpath), amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) (Neuro 4-Plex E). Analysis with a linear mixed model (SAS, PROC MIXED) revealed a significant effect of time of day for p-tau217, Aβ40, Aβ42, and NfL, and a significant effect of participant group for p-tau217. For p-tau217, lowest levels were observed in the morning upon waking and highest values in the afternoon/early evening. The magnitude of the diurnal variation for p-tau217 was similar to the reported increase in p-tau217 over one year in amyloid-β-positive mild cognitively impaired people. Currently, the factors driving this diurnal variation are unknown and could be related to sleep, circadian mechanisms, activity, posture, or meals. Overall, this work implies that time of day of sample collection may be relevant in the implementation and interpretation of plasma biomarkers in dementia research and care.

中文翻译：

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P-tau217 和其他痴呆症血液生物标志物：随时间的变化

痴呆症的血浆生物标志物，包括磷酸化 tau (p-tau217)，有望成为诊断、临床试验分层、监测疾病进展以及评估阿尔茨海默病患者干预措施成功与否的工具。然而，目前尚不清楚这些痴呆生物标志物水平是否随一天中的时间而变化，这可能对其临床价值产生影响。在两个方案中，我们在 27 小时的实验室方案中研究了 38 名参与者（70.8 ± 7.6 岁；平均值 ± 标准差），其中间隔 12 小时采集两次样本，或者在存在睡眠觉醒的情况下，在 24 小时内每 3 小时采集一次血液样本循环。研究人群包括轻度阿尔茨海默病患者 (PLWA，n = 8)、PLWA 的伴侣/照顾者 (n = 6) 和认知能力完好的老年人 (n = 24)。采用单分子阵列技术测量磷酸化 tau (p-tau217) (ALZpath)、淀粉样蛋白 β 40 (Aβ40)、淀粉样蛋白 β 42 (Aβ42)、胶质纤维酸性蛋白 (GFAP) 和神经丝光 (NfL)。神经 4-Plex E）。线性混合模型（SAS、PROC MIXED）分析揭示了一天中的时间对 p-tau217、Aβ40、Aβ42 和 NfL 的显着影响，以及参与者组对 p-tau217 的显着影响。对于 p-tau217，在早上醒来时观察到最低水平，在下午/傍晚观察到最高水平。p-tau217 的昼夜变化幅度与报道的β-淀粉样蛋白阳性轻度认知障碍人群一年内 p-tau217 的增加相似。目前，驱动这种昼夜变化的因素尚不清楚，可能与睡眠、昼夜节律机制、活动、姿势或膳食有关。总体而言，这项工作意味着一天中的样本采集时间可能与痴呆症研究和护理中血浆生物标志物的实施和解释相关。