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Article type: Research Article
Authors: Sancesario, Giulia Mariaa; b | Di Lazzaro, Giuliac | Alwardat, Mohammadc | Biticchi, Benedettab | Basile, Valeriob | Salimei, Chiarac | Colona, Vito Luigic | Sinibaldi Salimei, Paolad | Bernardini, Sergioc | Mercuri, Nicola Biagioa; c | Pisani, Antonioa; c | Schirinzi, Tommasoc; *
Affiliations: [a] IRCCS Fondazione Santa Lucia, Rome, Italy | [b] Department of Experimental Medicine and Surgery, University of Roma Tor Vergata, Rome, Italy | [c] Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy | [d] Department of Biomedicine and Prevention, University of Roma Tor Vergata, Rome, Italy
Correspondence: [*] Correspondence to: Tommaso Schirinzi, MD, PhD, Department of Systems Medicine, Unit of Neurology University of Roma Tor Vergata, Via Montpellier, 00133 Rome, Italy. Tel.: 0039 06 72596010; E-mail: [email protected].
Abstract: Background:Synaptopathy is critical in pathophysiology of Parkinson’s disease (PD). Cerebrospinal fluid (CSF) levels of neurogranin (NG) and amyloid-β42 (Aβ42) are considered markers of synaptic dysfunction in neurodegenerative diseases. Objective:To evaluate the CSF synaptopathy-related biomarkers, especially the novel Aβ42/NG ratio, in PD, establishing possible associations with cognitive level and other clinical parameters. Methods:Levels of NG, Aβ42, amyloid-β40, total and phosphorylated tau, and Aβ42/NG ratio were measured in 30 PD patients and 30 controls and correlated with cognitive and motor parameters. The accuracy in distinguishing the cognitive status was determined. Results:NG and Aβ42 were significantly reduced in PD, with higher NG levels in patients with worse cognition. The Aβ42/NG ratio showed a direct correlation with Mini-Mental State Examination, independently from age and sex, and differentiated cognitively impaired patients with 92% sensitivity and 71.4% specificity, accuracy higher than NG alone. No correlations resulted with motor disturbances or therapy. Conclusions:The novel Aβ42/NG ratio couples either presynaptic or postsynaptic markers of synaptic dysfunction, representing a potential global index of synaptopathy, useful to track cognitive functions in PD.
Keywords: Cerebrospinal fluid biomarkers, cognitive, neurogranin, Parkinson’s disease
DOI: 10.3233/JAD-200344
Journal: Journal of Alzheimer's Disease, vol. 76, no. 3, pp. 1171-1178, 2020
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