Study Rationale: Progressive aggregation of alpha-synuclein and the subsequent loss of affected brain cells starts 10 to 20 years before the onset of Parkinson’s disease (PD) symptoms. Early diagnosis and treatment of PD would therefore benefit from a test that detects alpha-synuclein aggregation in the brain. One such test, called a seed amplification assay (SAA), can detect alpha-synuclein aggregates. However, the current methods vary widely and are thus challenging to implement and standardize across different laboratories. In this project, we will compare the assay we developed to the commercial Amprion assay to facilitate harmonization of protocols and interlaboratory reproducibility.
Hypothesis: We hypothesize that we can achieve a robust compatibility between these two assay methods in a large number of people with PD and those at risk of developing PD, which will bring us one-step closer to moving this assay into a clinical setting.
Study Design: We will compare our in-house assay to commercial Amprion assay in cerebrospinal fluid samples from longitudinally followed individuals with PD and isolated REM sleep behaviour disorder (iRBD) from the Oxford Discovery cohort and clinico-pathological OPTIMA cohort. In addition, we will carry out our in-house SAA method in two longitudinally followed at-risk cohorts including people with iRBD and those with with mild cognitive impairment to further examine the use of SAA as predictive biomarker. Finally, we will assess how the SAA characteristics relate to clinical and pathological disease progression and other concomitant Alzheimer-type pathologies.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, a robust alpha-synuclein SAA can provide a simple, reliable diagnostic tool for PD at the earliest stages, even before the symptoms appear. The measurable data may also be useful to monitor disease progression and the effectiveness of future neuroprotective treatments of PD.
Next Steps for Development: With a robust, preclinical biomarker, we will have a greater window of time to conduct therapeutic trials of disease-modifying drugs and to possibly prevent PD in those destined to develop it, given that therapies could potentially be delivered prior to symptom onset.