Objective: Evaluate measurement of neurofilament light chain (NfL) in dried plasma spot cards, and to compare these to measurements using more invasive and in person sampling techniques.

Background: Neurofilament light chain is a plasma biomarker with widespread relevance in multiple neurodegenerative diseases.[1,2] Dried plasma spot (DPS) cards allow a participant to remotely collect a capillary blood plasma sample at home, and may offer various advantages over in-person collections for plasma NfL measurement.

Method: Finger-prick DPS (fDPS) and matched venous blood samples were collected from people with PD, people with multiple sclerosis (MS) and controls, with CSF samples collected in a subset of MS patients. DPS discs were inspected for quality, ensuring they were fully saturated with plasma and checking for the presence of any blood. Discs of poor quality were excluded from the analysis. DPS discs were eluted in 100μL elution buffer, shaken overnight (4°C, 400 rpm) and centrifuged for 10 minutes at 2000g before NfL was measured in duplicate using the MSD S-Plex NfL kit.

Results: Of the 97 fDPS collected, 89 (91.8%) were of an acceptable quality to be used in analyses. A strong correlation was observed between plasma/serum and DPS NfL (R2 = 0.721, p < 0.001; n = 55). A correlation was also observed between plasma/serum and CSF NfL (R2 = 0.451, p < 0.001; n = 25), and DPS and CSF NfL (R2 = 0.221, p = 0.027; n =22). Finger-prick DPS results were, on average, around 11% of the plasma/serum results, and 2% of the CSF results.

Conclusion: DPS results correlate with both matched venous plasma/serum and matched CSF samples. Previous studies have demonstrated a strong correlation between DPS and plasma results when plasma is applied to a DPS sampling card using a pipette.[3,4] To the best of our knowledge, ours is the largest study to date on examining the correlation between venous plasma/serum NfL and finger-prick DPS NfL, and the first to demonstrate a correlation between finger-prick DPS and CSF NfL.

It is encouraging to observe a strong correlation between DPS and venous plasma/serum NfL, given that the finger-prick DPS were of varying qualities. This implies that even in the ‘real world’ setting, the measurement of NfL using DPS should remain robust. DPS NfL results, however, remain much lower than the concentrations observed for venous blood and CSF NfL which remains an obstacle that needs to be overcome.

CSF, plasma, and DPS neurofilament light results

References: [1] Mollenhauer, B. et al. Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson’s Disease Progression. Mov. Disord. 35, 1999–2008 (2020).
[2] Palermo, G. et al. Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases. Mol. Neurobiol. 1–25 (2020).
[3] Lombardi, V. et al. The potential of neurofilaments analysis using dry-blood and plasma spots. Sci. Rep. 10, 97 (2020).
[4] Simrén, J., Ashton, N. J., Blennow, K. & Zetterberg, H. Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions. Alzheimers Dement. Diagn. Assess. Dis. Monit. 13, e12145 (2021).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dried-plasma-spot-cards-for-measurement-of-neurofilament-light-chain/