Claudia Alberti
Neurofilament light chain as clinical plasma biomarker of Charcot-Marie-Tooth disease
Autori
- CLAUDIA ALBERTI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – NEUROLOGY)
- DOMENICA SACCOMANNO (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – )
- ALESSIA ANASTASIA (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- GRAZIA D’ANGELO (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – )
- MARIA TERESA BASSI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – )
- LORENZO QUETTI (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- LUCA SALI (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- LORENZO BRAMBILLA (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- ALBERTO ROMANO (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- GIACOMO PIETRO COMI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY; NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- FEDERICA RIZZO (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- STEFANIA CORTI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.; NEUROMUSCULAR AND RARE DISEASES UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
- ELENA ABATI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.; NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
Presentatore
CLAUDIA ALBERTI
Modalità
Oral Communication
Abstract
Introduction: Charcot-Marie-Tooth disease type 2A (CMT2A) is an inherited sensory-motor peripheral neuropathy caused by mutations in the Mitofusin2 (MFN2) gene. Unfortunately, no curative treatment is available. Blood biomarkers are accessible and low-cost tools that may guide diagnosis and monitor progression. Neurofilament light chain (NfL) is a neuronal cytoplasmic protein abundant in neuronal axons, and released into the blood proportionally to the degree of axonal damage.
Materials and Methods: We collected serum from CMT2A (n=12), amyotrophic lateral sclerosis (ALS; n=10) and spinal muscular atrophy (SMA) type 3 (n=6) patients and from non-neurological controls (n=10. Additionally, we collected serum from wild-type (C57BL/6J) and transgenic mice expressing the R94Q mutation in the MFN2 gene under the Thy1.2 promoter (C57BL/6J Tg(Thy1-MFN2*R94Q)44Balo/J), at 5 months of age.
Results: We observed significantly higher NfL values in CMT2A patients compared to control. NfL levels were also significantly higher compared to untreated SMA type 3 patients and significantly lower compared to ALS patients. NfL values in CMT2A correlated negatively with age and disease duration. Analyses performed in mice showed similar results.
Conclusions: We observed higher NfL levels in CMT2A patients compared to controls. In addition, we observed significantly different values in CMT2A patients compared to patients with SMA type 3 and ALS, two mimickers of late-onset CMT2A, representing a potentially useful diagnostic biomarker. NfL levels seem to be higher in younger CMT2A patients and in those with a shorter disease duration, reflecting a more aggressive disease subtype. Similar results were observed in mouse models.