Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (8): 2373-2381.doi: 10.4103/NRR.NRR-D-23-01983

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Lifang Zhao1, 2, #, Mingkai Zhang3, #, Qimeng Li1, 2, Xuemin Wang1, 2, Jie Lu4, 5, 6, *, Ying Han3, 7, 8, 9, 10, *, Yanning Cai1, 2, 6, 11, *   

  1. 1 Department of Clinical Biobank, Xuanwu Hospital, Capital Medical University, Beijing, China;  2 Beijing Geriatric Medical Research Center, Beijing, China;  3 Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China;  4 Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China;  5 Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China;  6 Key Laboratory of Neurodegenerative diseases, Ministry of Education, Beijing, China;  7 School of Biomedical Engineering, Hainan University, Haikou, Hainan Province, China;  8 Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China;  9 National Clinical Research Center for Geriatric Diseases, Beijing, China;  10Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Gaoke Innovation Center, Shenzhen, Guangdong Province, China;  11Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China
  • Online:2025-08-15 Published:2024-12-14
  • Contact: Jie Lu, MD, PhD, imaginglu@hotmail.com; Ying Han, MD, PhD, hanying@xwh.ccmu.edu.cn; Yanning Cai, Ph.D, yanningcaimailbox@163.com.
  • Supported by:
    The study was supported by the National Key Research & Development Program of China, Nos. 2021YFC2501205 (to YC), 2022YFC24069004 (to JL), the STI2030-Major Project, Nos. 2021ZD0201101 (to YC), 2022ZD0211800 (to YH); the National Natural Science Foundation of China (Major International Joint Research Project), No. 82020108013 (to YH), the Sino-German Center for Research Promotion, No. M-0759 (to YH); and a grant from Beijing Municipal Science & Technology Commission (Beijing Brain Initiative), No. Z201100005520018 (to JL).

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Abstract: 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.

Key words: Alzheimer’s disease,  amyloid-β,  diagnostic ability,  glial fibrillary acidic protein,  neurodegeneration,  neurofilament light chain,   plasma biomarkers,  single molecule array,  storage time, tau