Brain and Cerebrospinal Fluid a-Synuclein Real-Time Quaking-Induced Conversion Identifies Lewy Body Pathology in LRRK2-PD

被引：17
作者：
Garrido, Alicia [1 ,2 ,3 ]
Fairfoul, Graham [4 ]
Tolosa, Eduardo [2 ,3 ,5 ]
Marti, Maria J. [2 ,3 ]
Ezquerra, Mario [1 ,2 ]
Green, Alison J. E. [4 ]
机构：
[1] Hosp Clin Barcelona, Inst Clin Neurociencies, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain
[2] Univ Barcelona, Inst Invest Biomed August Pi Sunyer i, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Spain
[3] Ctr Networked Biomed Res Neurodegenerat Dis CIBERN, Barcelona, Spain
[4] Univ Edinburgh, Ctr Clin Brain Sci, Natl CJD Res & Surveillance Unit, Edinburgh, Scotland
[5] Univ Barcelona, Inst Invest Biomed August Pi Sunyer i, C-Villarroel170, Barcelona 08036, Spain
来源：
MOVEMENT DISORDERS | 2023年 / 38卷 / 02期
关键词：
Parkinson's disease; LRRK2; alpha-synuclein; RT-QuIC; Lewy body; LRRK2-ASSOCIATED PARKINSONS-DISEASE; AUTOSOMAL-DOMINANT PARKINSONISM; ALPHA-SYNUCLEIN; CLINICAL-FEATURES; R1441G MUTATION; NEUROPATHOLOGY; GENE; PHENOTYPE; DIAGNOSIS; GENOTYPE;
D O I：
10.1002/mds.29284
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Background: The neuropathology of Parkinson's disease (PD) associated with leucine-rich repeat kinase 2 (LRRK2) mutations (LRRK2-PD) is heterogeneous and varies with the type of mutation. There are only a few studies evaluating seeding aggregation assays to detect alpha-synuclein (alpha-syn) in patients with LRRK2-PD. Objective: We aimed to investigate whether alpha-syn real-time quaking induced conversion (RT-QuIC) is a sensitive biomarker of synucleinopathy in LRRK2-PD.MethodsWe studied alpha-syn RT-QuIC in brain tissue and postmortem ventricular cerebrospinal fluid (CSF) of LRRK2-PD cases with and without Lewy-type pathology. Results: The accuracy of alpha-syn RT-QuIC in substantia nigra and CSF samples of patients with LRRK2-PD was 100%. The test also obtained 100% sensitivity to detect misfolded alpha-syn in substantia nigra of cases with idiopathic PD and was negative in the substantia nigra of all the control brains without Lewy-type pathology. Conclusions: Substantia nigra and ventricular CSF RT-QuIC discriminates with high sensitivity and specificity LRRK2 cases with Lewy-type pathology from those without it. RT-QuIC assay could be of particular interest in the selection of cases for clinical trials in this genetic form of PD. (C) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
引用
收藏
页码：333 / 338
页数：6
相关论文
共 37 条
[1]   Clinical features of LRRK2-associated Parkinson's disease in Central Norway [J].
Aasly, JO ;
Toft, M ;
Fernandez-Mata, I ;
Kachergus, J ;
Hulihan, M ;
White, LR ;
Farrer, M .
ANNALS OF NEUROLOGY, 2005, 57 (05) :762-765
[2]   α-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies [J].
Bongianni, Matilde ;
Ladogana, Anna ;
Capaldi, Stefano ;
Klotz, Sigrid ;
Baiardi, Simone ;
Cagnin, Annachiara ;
Perra, Daniela ;
Fiorini, Michele ;
Poleggi, Anna ;
Legname, Giuseppe ;
Cattaruzza, Tatiana ;
Janes, Francesco ;
Tabaton, Massimo ;
Ghetti, Bernardino ;
Monaco, Salvatore ;
Kovacs, Gabor G. ;
Parchi, Piero ;
Pocchiari, Maurizio ;
Zanusso, Gianluigi .
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2019, 6 (10) :2120-2126
[3]   Staging of brain pathology related to sporadic Parkinson's disease [J].
Braak, H ;
Del Tredici, K ;
Rüb, U ;
de Vos, RAI ;
Steur, ENHJ ;
Braak, E .
NEUROBIOLOGY OF AGING, 2003, 24 (02) :197-211
[4]   Clinical and Pathological Characteristics of Patients with Leucine-Rich Repeat Kinase-2 Mutations [J].
Covy, Jason P. ;
Yuan, Wuxing ;
Waxman, Elisa A. ;
Hurtig, Howard I. ;
Van Deerlin, Vivianna M. ;
Giasson, Benoit I. .
MOVEMENT DISORDERS, 2009, 24 (01) :32-39
[5]   Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies [J].
Fairfoul, Graham ;
McGuire, Lynne I. ;
Pal, Suvankar ;
Ironside, James W. ;
Neumann, Juliane ;
Christie, Sharon ;
Joachim, Catherine ;
Esiri, Margaret ;
Evetts, Samuel G. ;
Rolinski, Michal ;
Baig, Fahd ;
Ruffmann, Claudio ;
Wade-Martins, Richard ;
Hu, Michele T. M. ;
Parkkinen, Laura ;
Green, Alison J. E. .
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2016, 3 (10) :812-818
[6]   A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1 [J].
Funayama, M ;
Hasegawa, K ;
Kowa, H ;
Saito, M ;
Tsuji, S ;
Obata, F .
ANNALS OF NEUROLOGY, 2002, 51 (03) :296-301
[7]   LRRK2 mutations in Spanish patients with Parkinson disease -: Frequency, clinical features, and incomplete penetrance [J].
Gaig, C ;
Ezquerra, M ;
Marti, MJ ;
Muñoz, E ;
Valldeoriola, F ;
Tolosa, E .
ARCHIVES OF NEUROLOGY, 2006, 63 (03) :377-382
[8]   Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration [J].
Gaig, Carles ;
Ezquerra, Mario ;
Marti, Maria Jose ;
Valldeoriola, Francesc ;
Munoz, Esteban ;
Llado, Albert ;
Rey, Maria Jesus ;
Cardozo, Adriana ;
Molinuevo, Jose Luis ;
Tolosa, Eduardo .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2008, 270 (1-2) :94-98
[9]   α-synuclein RT-QuIC in cerebrospinal fluid of LRRK2-linked Parkinson's disease [J].
Garrido, Alicia ;
Fairfoul, Graham ;
Tolosa, Eduardo S. ;
Jose Marti, Maria ;
Green, Alison ;
Compta, Yaroslau ;
Valldeoriola, Francesc ;
Munoz, Esteban ;
Fernandez, Manel ;
Alvarez, Ramiro ;
Vilas, Dolores ;
Ispierto, Lourdes ;
De Fabregues, Oriol ;
Hernandez-Vara, Jorge ;
Puente, Victor ;
Calopa, Matilde ;
Jauma, Serge ;
Campdelacreu, Jaume ;
Bayes, Angels ;
Avila, Asuncion ;
Caballol, Nuria ;
Aguilar, Miguel ;
Casquero, Pilar .
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2019, 6 (06) :1024-1032
[10]   Multiple Organ Involvement by Alpha-Synuclein Pathology in Lewy Body Disorders [J].
Gelpi, Ellen ;
Navarro-Otano, Judith ;
Tolosa, Eduardo ;
Gaig, Carles ;
Compta, Yaroslau ;
Jesus Rey, Maria ;
Jose Marti, Maria ;
Hernandez, Isabel ;
Valldeoriola, Francesc ;
Rene, Ramon ;
Ribalta, Teresa .
MOVEMENT DISORDERS, 2014, 29 (08) :1010-1018
1234