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Updated: Aug 18, 2025
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Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
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Brain and Cerebrospinal Fluid α-Synuclein Real-Time Quaking-Induced Conversion Identifies Lewy Body Pathology in
Alicia Garrido1,2,3, Graham Fairfoul4, Eduardo Tolosa2,3
1Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain.
Summary
Alpha-synuclein (α-syn) real-time quaking induced conversion (RT-QuIC) accurately detects synucleinopathy in LRRK2-PD. This assay shows high sensitivity and specificity, aiding in LRRK2-PD diagnosis and clinical trial selection.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Genetics
Background:
- Neuropathology in Parkinson's disease (PD) linked to LRRK2 mutations (LRRK2-PD) is diverse.
- Limited research exists on detecting alpha-synuclein (α-syn) aggregation using seeding assays in LRRK2-PD patients.
Purpose of the Study:
- To evaluate alpha-synuclein (α-syn) real-time quaking induced conversion (RT-QuIC) as a sensitive biomarker for synucleinopathy in LRRK2-PD.
- To assess the diagnostic accuracy of α-syn RT-QuIC in LRRK2-PD.
Main Methods:
- Investigated α-syn RT-QuIC in brain tissue and postmortem cerebrospinal fluid (CSF) from LRRK2-PD cases.
- Included LRRK2-PD cases with and without Lewy-type pathology for analysis.
Main Results:
- α-syn RT-QuIC demonstrated 100% accuracy in substantia nigra and CSF samples from LRRK2-PD patients.
- The assay achieved 100% sensitivity for detecting misfolded α-syn in idiopathic PD substantia nigra.
- RT-QuIC was negative in control brains lacking Lewy-type pathology.
Conclusions:
- RT-QuIC in substantia nigra and CSF effectively differentiates LRRK2-PD with Lewy-type pathology from those without.
- The RT-QuIC assay holds potential for selecting participants in LRRK2-PD clinical trials.
