The field of cerebrospinal fluid (CSF) and plasma-based biomarkers in Alzheimer disease (AD) is advancing quickly. These biomarkers are being included in current guidelines and recommendations to biologically diagnose AD. However, reliable and reproducible measurements within and across different centers worldwide are necessary for the implementation of these markers in clinical routines. The reliability of such measurements is influenced, to some extent, by pre-analytical confounding factors (i.e., factors associated with sample collection, processing, and storage). These factors have been thoroughly evaluated for the measurements of the core AD CSF biomarkers and are currently being evaluated for their plasma counterparts. Results from such scientific efforts are compiled in CSF-based or plasma-based standardized operating procedures (SOPs) that are advised to be followed by centers assessing the biomarkers, thereby minimizing the variability of biomarker measurements. We here jointly review the available literature on the effect of different pre-analytical factors and the most updated recommendations for the measurements of the core biomarkers for AD (amyloid beta peptides, total and phosphorylated forms of Tau) and related processes i.e., neurofilament light as a marker associated with neurodegenerative processes, or glial fibrillary acidic protein as a marker associated with astrogliosis, in CSF and blood. We also review the impact of some pre-analytical factors on the CSF and plasma proteome using technologies employed for discovery of novel potential biofluid biomarkers. Lastly, we describe ongoing international initiatives aiming to standardize CSF- and blood-based neurodegenerative biomarker measurements. Understanding the impact of the different pre-analytical factors on biomarker measurements and compliance with consensus guidelines will facilitate the implementation of AD biomarkers in the clinical diagnostic workup.

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Impact of Pre-analytical Factors on Fluid Biomarker Measurements in Alzheimer Disease

  • Javier Torres-Torronteras,
  • Mariam Gouda,
  • Charlotte E. Teunissen,
  • Inge M. W. Verberk,
  • Marta del Campo

摘要

The field of cerebrospinal fluid (CSF) and plasma-based biomarkers in Alzheimer disease (AD) is advancing quickly. These biomarkers are being included in current guidelines and recommendations to biologically diagnose AD. However, reliable and reproducible measurements within and across different centers worldwide are necessary for the implementation of these markers in clinical routines. The reliability of such measurements is influenced, to some extent, by pre-analytical confounding factors (i.e., factors associated with sample collection, processing, and storage). These factors have been thoroughly evaluated for the measurements of the core AD CSF biomarkers and are currently being evaluated for their plasma counterparts. Results from such scientific efforts are compiled in CSF-based or plasma-based standardized operating procedures (SOPs) that are advised to be followed by centers assessing the biomarkers, thereby minimizing the variability of biomarker measurements. We here jointly review the available literature on the effect of different pre-analytical factors and the most updated recommendations for the measurements of the core biomarkers for AD (amyloid beta peptides, total and phosphorylated forms of Tau) and related processes i.e., neurofilament light as a marker associated with neurodegenerative processes, or glial fibrillary acidic protein as a marker associated with astrogliosis, in CSF and blood. We also review the impact of some pre-analytical factors on the CSF and plasma proteome using technologies employed for discovery of novel potential biofluid biomarkers. Lastly, we describe ongoing international initiatives aiming to standardize CSF- and blood-based neurodegenerative biomarker measurements. Understanding the impact of the different pre-analytical factors on biomarker measurements and compliance with consensus guidelines will facilitate the implementation of AD biomarkers in the clinical diagnostic workup.