This protein, known as alpha-synuclein, forms sticky clumps known as Lewy bodies within the brain cells of patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). There is currently no definitive test that allows doctors to determine if someone has Parkinson's or related disorders, especially at the early stage. So at present the diagnosis is based purely on clinical symptoms and can only be confirmed with a post-mortem examination of the brain.
These are hugely promising results and we are extending the analysis to a larger cohort of OPDC Discovery samples. We are particularly keen to understand how early these changes can be detected and whether our assay could be used as a predictive test. We also hope to refine our technique to detect alpha-synuclein aggregation in the nasal mucosa collected through a safer and less invasive brushing procedure compared to lumbar puncture required for the CSF collection.- Laura Parkkinen
Previous efforts to develop a test for alpha-synuclein have produced inconsistent results because the protein is also found in the brain and cerebrospinal fluid (CSF) of healthy subjects. It is only when the protein clumps together that it causes problems.
An extremely sensitive technology called real-time quaking-induced conversion (RT-QuIC) allows the measurement of stickiness of proteins; this approach has already been used to detect the CSF prion protein in Creutzfeldt-Jakob disease. Dr Laura Parkkinen and her team used this technology in brain material derived from the Oxford Brain Bank and CSF samples from the OPDC Discovery cohort. They were able to detect 'sticky' alpha-synuclein protein in the patients with PD and DLB with sensitivities of 95% and 92%, respectively, and with an overall specificity of 100% when compared to Alzheimer’s and controls.
Interestingly, few patients known to be at risk of developing PD/DLB (i.e. patients with REM sleep behaviour disorder) had a positive result. This suggests that this test could potentially detect patients before their motor and/or cognitive symptoms appear and thus allow the initiation of early treatment that could slow or even stop the disease.