Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions

Joel Simrén; Nicholas J Ashton; Kaj Blennow; Henrik Zetterberg

doi:10.1002/dad2.12145

Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions

Alzheimers Dement (Amst). 2021 Feb 20;13(1):e12145. doi: 10.1002/dad2.12145. eCollection 2021.

Authors

Joel Simrén^{1

2}, Nicholas J Ashton^{1

3

4

5}, Kaj Blennow^{1

2}, Henrik Zetterberg^{1

2

6

7}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy University of Gothenburg Mölndal Sweden.
² Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden.
⁴ King's College London, Institute of Psychiatry, Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute London UK.
⁵ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation London UK.
⁶ UK Dementia Research Institute at UCL London UK.
⁷ Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square London UK.

Abstract

Introduction: This study investigated alternative pre-analytical handling of blood for neurofilament light (NfL) analysis where resources are limited.

Method: Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48-hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters.

Results: Delayed centrifugation (R² = 0.991) and DPS (discovery cohort, R²= 0.954; confirmatory cohort, DPS: R² = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R² = 0.995) and shaking (R² = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS.

Discussion: DPS or delayed centrifugation are viable pre-analytical procedures for the accurate quantification of plasma NfL.

Keywords: dried blood spots; dried plasma spots; neurofilament light; pre‐analytical handling.