Tommaso Schirinzi1, Giulia Maria Sancesario2, Giulia Di Lazzaro3, Benedetta Biticchi4, Vito Luigi Colona3, Nicola Biagio Mercuri5, Sergio Bernardini4, Antonio Pisani5. 1. Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy. Electronic address: t.schirinzi@yahoo.com. 2. IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Experimental Medicine and Surgery, University of Roma Tor Vergata, Rome, Italy. 3. Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy. 4. Department of Experimental Medicine and Surgery, University of Roma Tor Vergata, Rome, Italy. 5. Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy.
Abstract
INTRODUCTION: Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD. METHODS: CSF levels of 42-amyloid-β, total and phosphorylated tau, α-synuclein and reciprocal ratios were measured in a group of 46 PD patients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features. RESULTS: We observed that α-synuclein levels were reduced in PD (p < 0.05, AUC = 0.8; p < 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p < 0.014; T = -3.6, p < 0.05; item 9: T = -2.1, p < 0.05, respectively). CONCLUSIONS: Our findings suggest that the reduction of CSF α-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF α-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.
INTRODUCTION: Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD. METHODS: CSF levels of 42-amyloid-β, total and phosphorylated tau, α-synuclein and reciprocal ratios were measured in a group of 46 PDpatients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features. RESULTS: We observed that α-synuclein levels were reduced in PD (p < 0.05, AUC = 0.8; p < 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p < 0.014; T = -3.6, p < 0.05; item 9: T = -2.1, p < 0.05, respectively). CONCLUSIONS: Our findings suggest that the reduction of CSF α-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF α-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.
Authors: Stephen Mullin; Laura Smith; Katherine Lee; Gayle D'Souza; Philip Woodgate; Josh Elflein; Jenny Hällqvist; Marco Toffoli; Adam Streeter; Joanne Hosking; Wendy E Heywood; Rajeshree Khengar; Philip Campbell; Jason Hehir; Sarah Cable; Kevin Mills; Henrik Zetterberg; Patricia Limousin; Vincenzo Libri; Tom Foltynie; Anthony H V Schapira Journal: JAMA Neurol Date: 2020-04-01 Impact factor: 18.302