- 1 September 2016
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| Positive RT-QuIC signal is only detected in the CSF of patients with pathologically confirmed alpha-synucleinopathy. ThT=thioflavine T; RFU= relative fluorescence unit |
Scientists from the Oxford Parkinson’s Disease Centre
(OPDC) and the Edinburgh Prion Unit have developed a new diagnostic test for
Parkinson’s disease. The test measures the 'stickiness' of a particular protein
in the cerebrospinal fluid.
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.
https://www.ndcn.ox.ac.uk/news/new-diagnostic-test-for-parkinson2019s-disease-moves-a-step-closer
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