Theme 7 Pre-clinical therapeutic strategies

Abstract

The rise of neurodegenerative disorders (NDD) in the ageing population is increasing demand on already stretched Health Services and is a major financial burden for society (1). The development of tools for early diagnosis is one of the responses to this problem (2). Cerebrospinal fluid (CSF) is the main repository of by-products of neuronal destruction (3); as serial lumbar punctures to procure CSF may be impractical in advanced patients (4), blood may represent the ideal source to track any meaningful disease signal of neurodegeneration.High-costs and low energy efficiency have pushed alternative means of samples collection and storage. Noviplex dried plasma spot (Np-DPS) and dried blood spot (DBS) on filter paper can be a remote, quick and inexpensive way of obtaining blood microsamples for the measurement of a large number of analytes in non-hospitalized, public health settings (5).We have used commercially-available and highly sensitive immunodetection assays (6) to test neurofilament light chain (Nf-L) expression in elute from DBS and from Np-DPS and compared these to standard Nf-L plasma measurement of healthy controls and patients with amyotrophic lateral sclerosis (ALS).We show that DBS and Np-DP cards can be used for remote blood collection and measurement of Nf-L. Nf-L measurement using elute from Noviplex DPS cards is equivalent to that obtained in plasma from the same blood samples, while levels of the same analyte in DBS elute are different, but provide discrimination between controls and ALS patients. Normalization using known loading protein concentration may also be needed for DBS analysis to adjust for the chromatographic effect of retained haemoglobin in the spot elute. Conversely, a simple elution step is required for Np-DPS, which reconstitutes a test fluid which is indistinguishable from plasma originated by conventional blood processing.