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


Por: Garrido, A, Fairfoul, G, Tolosa, ES, Marti, MJ, Green, A, Compta, Y, Valldeoriola, F, Munoz, E, Fernandez, M, Alvarez, R, Vilas, D, Ispierto, L, De Fabregues, O, Hernandez-Vara, J, Puente, V, Calopa, M, Jauma, S, Campdelacreu, J, Bayes, A, Avila, A, Caballol, N, Aguilar, M and Casquero, P

Publicada: 1 jun 2019
Resumen:
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.

Filiaciones:
Garrido, A:
 Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

 Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain

Fairfoul, G:
 Univ Edinburgh, Ctr Clin Brain Sci, Natl CJD Res & Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland

Tolosa, ES:
 Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain

 UB, Inst Invest Biomed August Pi & Sunyer IDIBAPS, C Villarroel 170, E-08036 Barcelona, Spain

Marti, MJ:
 Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

 Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain

 UB, Inst Invest Biomed August Pi & Sunyer IDIBAPS, C Villarroel 170, E-08036 Barcelona, Spain

Green, A:
 Univ Edinburgh, Ctr Clin Brain Sci, Natl CJD Res & Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland

Compta, Y:
 Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

Valldeoriola, F:
 Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

Munoz, E:
 Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

Fernandez, M:
 Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

:
 Hosp Badalona Germans Trias & Pujol, Neurol Serv, Barcelona, Spain

:
 Hosp Badalona Germans Trias & Pujol, Neurol Serv, Barcelona, Spain

Ispierto, L:
 Hosp Badalona Germans Trias & Pujol, Neurol Serv, Barcelona, Spain

De Fabregues, O:
 Hosp Univ Vall DHebron, Neurol Serv, Barcelona, Spain

Hernandez-Vara, J:
 Hosp Univ Vall DHebron, Neurol Serv, Barcelona, Spain

Puente, V:
 Hosp Del Mar, Neurol Serv, Barcelona, Spain

Calopa, M:
 Hosp Univ Bellvitge, Neurol Serv, Barcelona, Spain

Jauma, S:
 Hosp Univ Bellvitge, Neurol Serv, Barcelona, Spain

Campdelacreu, J:
 Hosp Univ Bellvitge, Neurol Serv, Barcelona, Spain

Bayes, A:
 Clin Teknon, Parkinsons Grp, Barcelona, Spain

Avila, A:
 Hosp St Joan dEspi Moises Broggi, Neurol Serv, Barcelona, Spain

Caballol, N:
 Hosp St Joan dEspi Moises Broggi, Neurol Serv, Barcelona, Spain

Aguilar, M:
 Hosp Univ Mutua de Terrasa, Neurol Serv, Barcelona, Spain

Casquero, P:
 Hosp Mateu Orfila, Menorca, Islas Baleares, Spain
ISSN: 23289503





Annals of Clinical and Translational Neurology
Editorial
John Wiley and Sons Inc., 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 6 Número: 6
Páginas: 1024-1032
WOS Id: 000471274100002
ID de PubMed: 31211166
imagen Green Published, gold

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