Long-Term Stability and Age-Dependence of Six Regulatory Serum Proteins

Abstract

Aim: The development of biomarker-based diagnostic procedures often relies on samples stored for several years. We aimed to investigate the influence of storage time and patient age on six neuroregulatory and immunoregulatory serum biomarkers. Materials & methods: We quantified six biomarkers in serum from 151 individuals using ELISA. Serum was stored at -80°C for up to 9.5 years. Results: When associating storage time with biomarker values, BDNF, VEGF-A and TGF-β1 showed a significant increase over time; IGF-1, MCP-1 and IL-18 did not. Associating participant age with biomarkers, only IL-18 in Alzheimer’s disease patients showed a significant increase. Conclusion: Storage time can influence results of biomarkers in human serum. This needs to be considered when assessing samples stored for several years.

Keywords:

• age-dependence
• Alzheimer’s disease
• biobanking
• biomarkers
• blood serum
• cognitive impairment
• long-term storage
• neuroinflammation
• neuroprotection
• storage time

Author contributions

F Menne and C Schipke were in equal parts responsible for conceptualization of the research question and hypotheses including extensive literature research. F Menne and C Schipke furthermore were responsible for statistical analyses and interpretation of the used data as well as creating graphs/tables and drafting and revising the original manuscript. C Clark was responsible for data curation and for drafting, reviewing and editing the manuscript. J Popp was responsible for funding acquisition, project administration and reviewing and editing the manuscript.

Acknowledgements

The authors want to thank all participants and their caregivers for contributing their data to this work.

Financial & competing interests disclosure

J Popp received consultation and speaker honoraria from Nestle Institute of Health Sciences, Innovation Campus, EPFL, Lausanne, Switzerland, Ono Pharma, OM Pharma Suisse and from Fujirebio Europe. C Schipke and F Menne are employees of Predemtec AG. This work was supported by grants from the Swiss National Research Foundation (to J Popp, SNF 320030_141179), Synapsis Foundation – Alzheimer Research Switzerland (to J Popp, grant no. 2017-PI01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.