Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Disea
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Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases Giovanni Palermo 1 & Sonia Mazzucchi 1 & Alessandra Della Vecchia 1 & Gabriele Siciliano 1 & Ubaldo Bonuccelli 1 & Carole Azuar 2,3 & Roberto Ceravolo 1 & Simone Lista 3,4,5 & Harald Hampel 3 & Filippo Baldacci 1,3 Received: 10 May 2020 / Accepted: 22 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract One of the most pressing challenges in the clinical research of neurodegenerative diseases (NDDs) is the validation and standardization of pathophysiological biomarkers for different contexts of use (CoUs), such as early detection, diagnosis, prognosis, and prediction of treatment response. Neurofilament light chain (NFL) concentration is a particularly promising candidate, an indicator of axonal degeneration, which can be analyzed in peripheral blood with advanced ultrasensitive methods. Serum/plasma NFL concentration is closely correlated with cerebrospinal fluid NFL and directly reflects neurodegeneration within the central nervous system. Here, we provide an update on the feasible CoU of blood NFL in NDDs and translate recent findings to potentially valuable clinical practice applications. As NFL is not a disease-specific biomarker, however, blood NFL is an easily accessible biomarker with promising different clinical applications for several NDDs: (1) early detection and diagnosis (i.e., amyotrophic lateral sclerosis, Creutzfeldt–Jakob disease, atypical parkinsonisms, sporadic late-onset ataxias), (2) prognosis (Huntington’s disease and Parkinson’s disease), and (3) prediction of time to symptom onset (presymptomatic mutation carriers in genetic Alzheimer’s disease and spinocerebellar ataxia type 3). Keywords Alzheimer’s disease . Amyotrophic lateral sclerosis . Biomarkers . Creutzfeldt–Jakob disease . NFL . Parkinsonian syndromes
Introduction Neurodegenerative diseases (NDDs) are currently considered as a continuum of disorders with common pathophysiological
* Filippo Baldacci [email protected] 1
Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
2
Centre National de Référence des Démences Rares ou Précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France
3
Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l’hôpital, F-75013, Paris, France
4
Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l’hôpital, F-75013 , Paris, France
5
Institute of Memory and Alzheimer’s Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l’hôpital, F-75013, Paris, France
mechanisms, including misfolded protein deposition, neuronal synaptic disruption, axonal degeneration, neuroinflammation, and oxidative stress [1–3]. Therefore, the greatest current challenge in the field of NDDs is to provide biomarkers for the pathological mechanisms underlying each
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