The potential of neurofilaments analysis using dry-blood and plasma spots.

Abstract

The lack of biomarkers for an early diagnosis of neurodegenerative disorders (NDs) has hampered the development of therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments light chain (Nf-L), an integral part of the axonal structure, has emerged as a robust fluid biomarker for fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs of samples collection/processing and cold-chain storage, we describe the measurement of Nf-L in blood fractions obtained from dry blood spots (DBS) and dry plasma spots (DPS), two filter paper-based remote blood collection tools. To test the feasibility of using this approach, Nf-L analysis in DBS/DPS is compared to that in plasma obtained from the same blood sample, looking at Nf-L discriminatory power in the clinical stratification of ALS compared to healthy controls. With the best pre-analytical treatment for total protein recovery and using highly sensitive immunoassays, we report the detection of different Nf-L levels in DBS elute compared to reference plasma and DPS from the same blood samples. However, Nf-L measurement in DBS elutes provides a very good discrimination of ALS from healthy controls which is comparable to that obtained using plasma Nf-L assays. With the available immunodetection methods, we show that Nf-L measurement based on DPS microsampling is similar to that in plasma. The filter-paper biophysical characteristics and the interference of high haemoglobin concentration released by erythrocyte lysis is likely to perturb Nf-L detection in DBS elute. Further studies into DBS-based Nf-L detection and its analytical optimization are needed to make this method suitable for routine Nf-L blood analyses in neurodegeneration.

• Authors: Vittoria Lombardi, Daniele Carassiti, Gavin Giovannoni, Ching-Hua Lu, Rocco Adiutori, Andrea Malaspina
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 97 (01 09 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 31919375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Neurofilament Proteins
• neurofilament protein L

Topics

• Aged
• Amyotrophic Lateral Sclerosis (blood, diagnosis)
• Biomarkers (blood)
• Blood Specimen Collection (methods)
• Case-Control Studies
• Dried Blood Spot Testing (methods)
• Female
• Humans
• Male
• Middle Aged
• Neurofilament Proteins (blood)
• Specimen Handling (methods)