Manuel Delgado-Alvarado1,2, Belén Gago1,2, Ana Gorostidi1,2,3, Haritz Jiménez-Urbieta1,2, Rosalía Dacosta-Aguayo1,2, Irene Navalpotro-Gómez1,2, Javier Ruiz-Martínez1,2,4, Alberto Bergareche1,2,4, José F Martí-Massó1,2,4, Pablo Martínez-Lage5, Andrea Izagirre5, María C Rodríguez-Oroz1,2,4,6,7. 1. Neurodegenerative Disorders Area, Biodonostia Health Research Institute, San Sebastián, Spain. 2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. 3. Genomics Platform, Biodonostia Research Institute, San Sebastián, Spain. 4. Movement Disorders Unit, Department of Neurology, University Hospital Donostia, San Sebastián, Spain. 5. Department of Neurology, CITA-Alzheimer Foundation, San Sebastián, Spain. 6. Ikerbasque (Basque Foundation for Science), Bilbao, Spain. 7. Basque Center on Cognition Brain and Language (BCBL), San Sebastián, Spain.
Abstract
BACKGROUND: No CSF or plasma biomarker has been validated for diagnosis or progression of PD. OBJECTIVES: To assess whether the CSF and plasma levels of proteins associated with PD neuropathological inclusions and with neuroinflammation might have value in the diagnosis of PD or in relation to disease severity. METHODS: CSF levels of α-synuclein, amyloid-ß1-42, total tau, and threonine-181 phosphorylated tau, as well as CSF and plasma levels of cytokines (interleukin-1ß, interleukin-2, interleukin, interferon-γ, and tumor necrosis factor α) were studied in 40 PD patients and 40 healthy controls. Plasma levels of cytokines were measured in 51 patients and 26 aditional controls. We also explored the Parkinson's Progression Markers Initiative data set as a replication cohort. RESULTS: CSF levels of α-synuclein, amyloid-ß1-42, and tumor necrosis factor α were lower in patients than in controls, and the total tau/α-synuclein, phosphorylated tau/α-synuclein, total tau/amyloid-ß1-42+α-synuclein, and phosphorylated tau/amyloid-ß1-42+α-synuclein ratios were higher in patients. The best area under the curve value was obtained for the phosphorylated tau/α-synuclein ratio alone (0.86) and also when this was combined with tumor necrosis factor α in CSF (0.91; sensitivity 92.9%, specificity 75% for a cut-off value of ≤ 0.71). Phosphorylated tau/α-synuclein and phosphorylated tau/amyloid-ß1-42+α-synuclein were higher in patients than in controls of the Parkinson's Progression Markers Initiative database. Plasma cytokines did not differ between groups, although interleukin-6 levels were positively correlated with UPDRS-I, -II, and -III scores. CONCLUSIONS: The CSF phosphorylated tau/α-synuclein ratio alone, and in combination with tumor necrosis factor α and plasma interleukin-6 levels, might serve as biomarkers to diagnose PD and monitor its severity.
BACKGROUND: No CSF or plasma biomarker has been validated for diagnosis or progression of PD. OBJECTIVES: To assess whether the CSF and plasma levels of proteins associated with PD neuropathological inclusions and with neuroinflammation might have value in the diagnosis of PD or in relation to disease severity. METHODS: CSF levels of α-synuclein, amyloid-ß1-42, total tau, and threonine-181 phosphorylated tau, as well as CSF and plasma levels of cytokines (interleukin-1ß, interleukin-2, interleukin, interferon-γ, and tumor necrosis factor α) were studied in 40 PDpatients and 40 healthy controls. Plasma levels of cytokines were measured in 51 patients and 26 aditional controls. We also explored the Parkinson's Progression Markers Initiative data set as a replication cohort. RESULTS: CSF levels of α-synuclein, amyloid-ß1-42, and tumor necrosis factor α were lower in patients than in controls, and the total tau/α-synuclein, phosphorylated tau/α-synuclein, total tau/amyloid-ß1-42+α-synuclein, and phosphorylated tau/amyloid-ß1-42+α-synuclein ratios were higher in patients. The best area under the curve value was obtained for the phosphorylated tau/α-synuclein ratio alone (0.86) and also when this was combined with tumor necrosis factor α in CSF (0.91; sensitivity 92.9%, specificity 75% for a cut-off value of ≤ 0.71). Phosphorylated tau/α-synuclein and phosphorylated tau/amyloid-ß1-42+α-synuclein were higher in patients than in controls of the Parkinson's Progression Markers Initiative database. Plasma cytokines did not differ between groups, although interleukin-6 levels were positively correlated with UPDRS-I, -II, and -III scores. CONCLUSIONS: The CSF phosphorylated tau/α-synuclein ratio alone, and in combination with tumor necrosis factor α and plasma interleukin-6 levels, might serve as biomarkers to diagnose PD and monitor its severity.
Authors: Diego Castillo-Barnes; Javier Ramírez; Fermín Segovia; Francisco J Martínez-Murcia; Diego Salas-Gonzalez; Juan M Górriz Journal: Front Neuroinform Date: 2018-08-14 Impact factor: 4.081
Authors: Catarina M Abreu; Ricardo Soares-Dos-Reis; Pedro N Melo; João B Relvas; Joana Guimarães; Maria José Sá; Andrea P Cruz; Inês Mendes Pinto Journal: Front Mol Neurosci Date: 2018-05-16 Impact factor: 5.639
Authors: José Luis Molinuevo; Scott Ayton; Richard Batrla; Martin M Bednar; Tobias Bittner; Jeffrey Cummings; Anne M Fagan; Harald Hampel; Michelle M Mielke; Alvydas Mikulskis; Sid O'Bryant; Philip Scheltens; Jeffrey Sevigny; Leslie M Shaw; Holly D Soares; Gary Tong; John Q Trojanowski; Henrik Zetterberg; Kaj Blennow Journal: Acta Neuropathol Date: 2018-11-28 Impact factor: 17.088