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
Green Published, gold
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