title: Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease.
abstract: There is a great interest in developing cerebrospinal fluid (CSF) biomarkers for diagnosis and prognosis of Parkinson's disease (PD). CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD diagnosis. Preliminary evidences show that the combination of CSF t-α-syn and classical Alzheimer's disease (AD) biomarkers-β-amyloid 1-42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau)-differentiate PD patients from controls, and that reduced levels of Aβ42 represent a predictive factor for development of cognitive deterioration in PD. In this prospective study carried out in 44 PD patients and 25 neurological controls we wanted to verify whether the combination of CSF α-synuclein species-t-α-syn and o-α-syn-and classical AD biomarkers may help in differentiating PD from neurological controls, and if these biomarkers may predict cognitive decline. The median of follow-up duration was 3 years (range: 2-6 years). Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used for monitoring cognitive changes along time, being administered once a year. Oligo/total α-syn ratio (o/t-α-syn ratio) confirmed its diagnostic value, significantly contributing to the discrimination of PD from neurological controls. A greater diagnostic accuracy was reached when combining o/t-α-syn and Aβ42/tau ratios (Sens = 0.70, Spec = 0.84, AUC = 0.82; PPV = 0.89, NPV = 0.62, LR+ = 4.40, DOR = 12.52). Low CSF Aβ42 level was associated with a higher rate of MMSE and MoCA decline, confirming its role as independent predictive factor for cognitive decline in PD. None of the other biomarkers assessed (t-tau, p-tau, t-α-syn and o-α-syn) showed to have prognostic value. We conclude that combination of CSF o/t-α-syn and Aβ42/tau ratios improve the diagnostic accuracy of PD. PD patients showing low CSF Aβ42 levels at baseline are more prone to develop cognitive decline.
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Farotti
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy ; Dipartimento di Epidemiologia, Regione Umbria Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Eusebi
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Sezione di Biochimica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Chiasserini
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: De Carlo
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Giannandrea
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvadori
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Lisetti
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Tambasco
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
authors.forename: Aroldo
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates.
authors.forename: Nour K
authors.initials: NK
authors.lastname: Majbour
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University Al Ain, United Arab Emirates ; Faculty of Medicine, King Abdulaziz University Jeddah, Saudi Arabia.
authors.forename: Omar
authors.initials: O
authors.lastname: El-Agnaf
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy ; IRCCS Fondazione S. Lucia Roma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
keywords: Aβ42; Parkinson's disease; alpha synuclein; cerebrospinal fluid biomarkers; cognitive decline; phosphorylated tau; total tau
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