Peripherin: a novel early diagnostic and prognostic plasmatic biomarker in Amyotrophic Lateral Sclerosis
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Background and aim
Motor neuron diseases (MND) are heterogeneous and complex neurodegenerative disorders. Biomarkers could facilitate early diagnosis, prognosis determination, and patient stratification. Among the most studied biomarkers are neurofilaments, with peripherin (PRPH), a specific type predominantly expressed in peripheral nervous system neurons, gaining attention. To date, no studies have evaluated PRPH levels in human plasma.
Methods
sandwich-ELISA was used to quantify plasma peripherin from 120 MND (100 ALS, 4 PMA, 15 PLS), 73 MND-mimics (including myelopathy, radiculopathy, axonal neuropathies, Hirayama disease, IBM, benign fasciculation syndrome, functional syndrome, myasthenia, post-polio syndrome) and 38 healthy-controls (HCs). Plasma was collected at the time of diagnosis or some months earlier. 41 ALS were evaluated longitudinally. ALSFRSr, MRC, spirometry, genetic tests, disease progression rate (PR), blood examinations, and neuropsychological tests were performed. Statistical analyses included Kruskal-Wallis, Mann-Whitney, Cox-regression, and Kaplan-Meier curves.
Results
PRPH plasma levels is different between groups (p<0.0001); Bonferroni’s correction shows higher PRPH in MND compared to MND-mimics and HCs. Comparing PLS with HSP PRPH resulted to be higher (p=0.0001). Differences are confirmed co-variating for age and sex. ROC curve shows a good capability of PRPH to discriminate ALS from MND mimics (AUC= 0.85).
PRPH levels correlated directly with ALSFRSr, and with lower body involvement while inversely with PR. Higher PRPH levels were associated with survival advantages.
Discussion
Plasma PRPH levels are elevated in MND, particularly ALS, from the early disease stages, distinguishing MND from mimics and correlating with clinical parameters and survival. Further multicentre studies incorporating additional biomarkers are required to refine the diagnostic and prognostic utility of PRPH in MND.
