Open Accessα ‐synuclein RT‐QuIC in cerebrospinal fluid of LRRK 2‐linked Parkinson's disease
Author(s) -
Garrido Alicia,
Fairfoul Graham,
Tolosa Eduardo S.,
Martí Maria José,
Green Alison
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.772
Subject(s) - lrrk2 , medicine , parkinsonism , parkinson's disease , neuropathology , cerebrospinal fluid , histopathology , pathology , gastroenterology , disease
Background Leucine‐rich kinase 2 ( LRRK 2)‐linked Parkinson's disease ( PD ) is clinically indistinguishable from idiopathic PD ( IPD ). A pleiotropic neuropathology has been recognized but the majority of studies in LRRK 2 p.G2019S patients reveal Lewy‐type synucleinopathy as its principal histological substrate. To date no in vivo biomarkers of synucleinopathy have been found in LRRK 2 mutation carriers. Objectives We used real‐time quaking‐induced conversion ( RT ‐Qu IC ) technique to assess the presence of alpha‐synuclein (a‐syn) aggregates in cerebrospinal fluid ( CSF ) of LRRK 2 p.G2019S carriers. Methods CSF samples of 51 subjects were analyzed: 15 LRRK 2 p.G2019S PD , 10 IPD , 16 LRRK 2 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) L RRK 2‐ PD , and 18.8% ( n = 3) LRRK2‐NMC had a positive a‐syn RT ‐Qu IC response. RT ‐Qu IC detected IPD with 90% sensitivity and 80% specificity. No clinical differences were detected between LRRK 2‐ PD patients with positive and negative RT ‐Qu IC . A positive RT ‐Qu IC result in LRRK 2‐ NMC occurred in a higher proportion of subjects meeting the Movement Disorder Society research criteria for prodromal PD . Interpretation RT ‐Qu IC detects a‐syn aggregation in CSF in a significant number of patients with LRRK 2‐ PD , but less frequently than in IPD . A small percentage of LRRK 2‐ 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 ‐Qu IC could contribute to the selection of candidates to receive disease modifying drugs, in particular treatments targeting a‐syn deposition.