Objective: The objective of this study was to investigate the relationship between plasma and dried blood/ plasma spot measurements of inflammatory markers (IFN-ɣ, IL-1β, IL-6, TNF-α) and NfL in participants at high risk of future PD and healthy controls (HCs).

Background: Recent evidence suggests that dried blood/ plasma spot cards can be used as alternatives to plasma for the measurement of peripheral inflammatory cytokines and neurofilament light chain (NfL) [1][2][3][4]; markers of interest for the prodromal detection of Parkinson’s disease (PD) [5][6][7].

Method: 28 patients with polysomnograph-confirmed rapid eye movement (REM) sleep behaviour disorder (RBD) and 27 age- and sex-matched HCs were recruited. For each participant, finger-prick dried blood spots and venous blood were collected, alongside clinical and demographic data. Venous dried blood spots (vDBS), venous dried plasma spots (vDPS) and plasma were prepared from the venous blood. Analysis of all biomarkers was carried out using the Meso Scale Discovery platform. Linear regression was used to compare sample types and the Mann-Whitney U test was used to compare biomarkers between the RBD and HC groups.

Results: Correlations were observed between vDBS and plasma for IFN-ɣ, IL-6, and TNF-α ([p < 0.0001, R² = 0.94], [p < 0.0001, R² = 0.56], and [p = 0.0002, R² = 0.36] respectively) and between vDPS and plasma for IFN-ɣ, IL-6, TNF-α, and NfL ([p < 0.0001, R2 = 0.92], [p < 0.0001, R² = 0.75], [p < 0.0001, R² = 0.43], and [p < 0.0001, R² = 0.46] respectively). No correlation was seen between vDBS/vDPS and plasma for IL-1β. Finger-prick dried blood spots also correlated with vDBS for IFN-ɣ, IL-6, and TNF-α ([p < 0.0001, R² = 0.93], [p = 0.001, R² = 0.57], and [p = 0.026, R² = 0.27] respectively). Plasma NfL and IL-6 levels were elevated in the RBD group compared to HCs with nominal significance (median: NfL [HC] = 61.53 pg/mL, [RBD] = 80.46 pg/mL, p = 0.032 and IL-6 [HC] = 0.86 pg/mL, [RBD] = 1.07 pg/mL, p = 0.035).

Conclusion: This pilot study suggests that remote sampling using dried blood/ plasma spots is feasible for measuring IFN-ɣ, IL-6, TNF-α, and NfL. IL-6 and NfL also appeared to be raised in RBD patients compared to HCs. Further studies are necessary to confirm these findings and to utilise remote sampling to investigate early biomarkers of PD and related disorders.

References: [1] McDade, T. W., Miller, A., Tran, T. T., Borders, A. E. B. & Miller, G. A highly sensitive multiplex immunoassay for inflammatory cytokines in dried blood spots. American Journal of Human Biology 33, e23558 (2021).
[2] Massaro, A. N. et al. Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy. Pediatr Res 85, 655–661 (2019).
[3] 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. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring 13, e12145 (2021).
[4] Lombardi, V. et al. The potential of neurofilaments analysis using dry-blood and plasma spots. Scientific reports 10, 1–12 (2020).
[5] Cheong, J. L. Y., de Pablo-Fernandez, E., Foltynie, T. & Noyce, A. J. The Association Between Type 2 Diabetes Mellitus and Parkinson’s Disease. Journal of Parkinson’s Disease 10, 775–789 (2020).
[6] Jensen, M. P. et al. Lower Lymphocyte Count is Associated With Increased Risk of Parkinson’s Disease. Annals of Neurology 89, 803–812 (2021).
[7] Mollenhauer, B. et al. Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson’s Disease Progression. Movement Disorders 35, 1999–2008 (2020).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dried-blood-and-plasma-spots-for-the-measurement-of-neurofilament-light-chain-and-inflammatory-cytokines-in-patients-with-rem-sleep-behaviour-disorder/