alpha-synuclein RT-QuIC in cerebrospinal fluid of LRRK2-linked Parkinson's disease

Background Leucine-rich kinase 2 (LRRK2)-linked Parkinson's disease (PD) is clinically indistinguishable from idiopathic PD (IPD). A pleiotropic neuropathology has been recognized but the majority of studies in LRRK2 p.G2019S patients reveal Lewy-type synucleinopathy as its principal histologic...

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Detalles Bibliográficos
Autores: Garrido, Alicia, Fairfoul, Graham, Tolosa, Eduard, Jose Marti, Maria, Green, Alison, Compta, Yaroslau, Valldeoriola, Francesc, Munoz, Esteban, Fernandez, Manuel, Alvarez, Ramiro, Vilas, Dolores, Ispierto, Lourdes, de Fabregues-Boixar, Oriol, Hernández Vara, Jorge, Puente, Victor, Calopa, Matilde, Jauma, Serge, Campdelacreu, Jaume, Bayes, Angels, Avila, Asuncion, Caballol, Nuria, Aguilar, Miquel, Casquero Subías, Pilar, Barcelona LRRK2 Study Grp
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/17213
Acceso en línea:https://hdl.handle.net/20.500.13003/17213
Access Level:acceso abierto
Palabra clave:Middle Aged
Cerebrospinal Fluid
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Humans
Parkinson Disease
Aged
alpha-Synuclein
Male
Biomarkers
Mutation
Adult
Female
Líquido Cefalorraquídeo
Humanos
Persona de Mediana Edad
Biomarcadores
Anciano
alfa-Sinucleína
Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina
Enfermedad de Parkinson
Femenino
Adulto
Mutación
Masculino
Descripción
Sumario:Background Leucine-rich kinase 2 (LRRK2)-linked Parkinson's disease (PD) is clinically indistinguishable from idiopathic PD (IPD). A pleiotropic neuropathology has been recognized but the majority of studies in LRRK2 p.G2019S patients reveal Lewy-type synucleinopathy as its principal histological substrate. To date no in vivo biomarkers of synucleinopathy have been found in LRRK2 mutation carriers. Objectives We used real-time quaking-induced conversion (RT-QuIC) technique to assess the presence of alpha-synuclein (a-syn) aggregates in cerebrospinal fluid (CSF) of LRRK2 p.G2019S carriers. Methods CSF samples of 51 subjects were analyzed: 15 LRRK2 p.G2019S PD, 10 IPD, 16 LRRK2 p.G2019S nonmanifesting carriers (NMC) and 10 healthy controls. The presence of parkinsonism and prodromal symptoms was assessed in all study subjects. Results Forty percent (n = 6) LRRK2-PD, and 18.8% (n = 3) LRRK2-NMC had a positive a-syn RT-QuIC response. RT-QuIC detected IPD with 90% sensitivity and 80% specificity. No clinical differences were detected between LRRK2-PD patients with positive and negative RT-QuIC. A positive RT-QuIC result in LRRK2-NMC occurred in a higher proportion of subjects meeting the Movement Disorder Society research criteria for prodromal PD. Interpretation RT-QuIC detects a-syn aggregation in CSF in a significant number of patients with LRRK2-PD, but less frequently than in IPD. A small percentage of LRRK2-NMC tested also positive. If appropriately validated in long-term studies with large number of mutation carriers, and hopefully, postmortem or in vivo confirmation of histopathology, RT-QuIC could contribute to the selection of candidates to receive disease modifying drugs, in particular treatments targeting a-syn deposition.

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