Zhao Lifang, Zhang Mingkai, Li Qimeng, Wang Xuemin, Lu Jie, Han Ying, Cai Yanning
Department of Clinical Biobank, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Geriatric Medical Research Center, Beijing, China.
Neural Regen Res. 2025 Aug 1;20(8):2373-2381. doi: 10.4103/NRR.NRR-D-23-01983. Epub 2024 Apr 16.
JOURNAL/nrgr/04.03/01300535-202508000-00027/figure1/v/2024-09-30T120553Z/r/image-tiff Several promising plasma biomarker proteins, such as amyloid-β (Aβ), tau, neurofilament light chain, and glial fibrillary acidic protein, are widely used for the diagnosis of neurodegenerative diseases. However, little is known about the long-term stability of these biomarker proteins in plasma samples stored at -80°C. We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort. Plasma samples from 229 cognitively unimpaired individuals, encompassing healthy controls and those experiencing subjective cognitive decline, as well as 99 patients with cognitive impairment, comprising those with mild cognitive impairment and dementia, were acquired from the Sino Longitudinal Study on Cognitive Decline project. These samples were stored at -80°C for up to 6 years before being used in this study. Our results showed that plasma levels of Aβ42, Aβ40, neurofilament light chain, and glial fibrillary acidic protein were not significantly correlated with sample storage time. However, the level of total tau showed a negative correlation with sample storage time. Notably, in individuals without cognitive impairment, plasma levels of total protein and tau phosphorylated protein threonine 181 (p-tau181)also showed a negative correlation with sample storage time. This was not observed in individuals with cognitive impairment. Consequently, we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time. Therefore, caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases, such as Alzheimer's disease. Furthermore, in cohort studies, it is important to consider the impact of storage time on the overall results.
《期刊》/nrgr/04.03/01300535 - 202508000 - 00027/图1/v/2024 - 09 - 30T120553Z/图像 - 标签图像文件格式 几种有前景的血浆生物标志物蛋白，如淀粉样β蛋白（Aβ）、tau蛋白、神经丝轻链和胶质纤维酸性蛋白，被广泛用于神经退行性疾病的诊断。然而，对于这些生物标志物蛋白在-80°C储存的血浆样本中的长期稳定性知之甚少。我们旨在通过一个大型队列研究来探索储存时间如何影响这些生物标志物的诊断准确性。从中国认知衰退纵向研究项目中获取了229名认知未受损个体的血浆样本，包括健康对照者和经历主观认知衰退者，以及99名认知障碍患者，包括轻度认知障碍和痴呆患者。这些样本在-80°C储存长达6年，然后用于本研究。我们的结果表明，Aβ42、Aβ40、神经丝轻链和胶质纤维酸性蛋白的血浆水平与样本储存时间无显著相关性。然而，总tau蛋白水平与样本储存时间呈负相关。值得注意的是，在无认知障碍个体中，总蛋白和苏氨酸181磷酸化tau蛋白（p - tau181）的血浆水平也与样本储存时间呈负相关。在认知障碍个体中未观察到这种情况。因此，我们推测血浆p - tau181以及p - tau181与总tau蛋白的比值的诊断准确性可能受样本储存时间影响。因此，在使用这些血浆生物标志物来识别神经退行性疾病（如阿尔茨海默病）时建议谨慎。此外，在队列研究中，考虑储存时间对总体结果的影响很重要。
