Lay summary by Emily Prescott, reviewed by Dr Scott Allen
Background
Parkinson’s Disease is characterised by the presence of Lewy bodies in the brain. Lewy bodies are clumps of protein, mainly made up of the toxic form of the protein ‘alpha-synuclein’. The current gold standard of diagnosing Parkinson’s Disease is detecting Lewy bodies in postmortem brain tissue. However, the formation of Lewy bodies happens over a long time-period and toxic alpha-synuclein is present in human brain fluid (known as cerebrospinal fluid or CSF) up to 10 years before symptom onset. A new test has been developed that can detect toxic alpha-synuclein in CSF and shows promise for the early diagnosis of Parkinson’s Disease.
Why is the study important?
Due to the challenge of diagnosing Parkinson’s Disease, health care professionals rely on a combination of patient’s symptoms and the individual’s medical history. This means diagnosis takes a long time, and usually happens at a late stage in disease when the damage has already been done. This study outlines a test which can aid early diagnosis of Parkinson’s Disease and could lead to earlier and more successful treatment.
What did the authors do and how did they do it?
This study uses a large group of individuals including Parkinson’s Disease patients, individuals at risk of developing Parkinson’s Disease, and healthy individuals. All individuals underwent assessment of clinical symptoms and gave samples of CSF.
In Parkinson’s Disease patients, toxic alpha-synuclein is present at very low amounts in the CSF and is hard to detect. The authors used a ‘seed amplification assay’ to increase any toxic alpha-synuclein to a detectable level. Within this test, toxic alpha-synuclein acts as a template which is extended to form a larger form of alpha-synuclein. This larger alpha-synuclein is then broken apart to generate a higher number of smaller toxic alpha-synuclein. This process increases the overall number of toxic alpha-synuclein to a detectable level, however if no toxic alpha-synuclein is present then there will be no detection. Using this test, researchers aim to discriminate between Parkinson’s Disease patients and healthy individuals.
Image: This test works by increasing the amount of toxic alpha-synuclein present in the CSF. Toxic alpha-synuclein acts as a template and is extended into a larger form, the larger alpha-synuclein is then broken apart to form a higher number of smaller toxic-alpha synuclein, this increased amount is detectable by the test.
What are the results?
The results show this test is highly accurate at diagnosing individuals with Parkinson’s Disease; 478 out of 545 Parkinson’s Disease patients received a positive result, compared to only 6 out of 163 healthy individuals. The test has shown to be more accurate for patients with a common early symptom of Parkinson’s Disease; a decreased sense of smell (379 out of 390 individuals had a positive result), and less accurate for patients without any problems with smell (91 out of 146 individuals had a positive result). Additionally, the test shows promise for diagnosing at risk individuals, with 44 out of 51 individuals having a positive result.
What do the findings mean going forward for people with the disease?
An early diagnostic test could lead to catching the disease before the damage is done and potentially more effective treatment. However, collection of CSF is an uncomfortable procedure, and so development of this test for use on blood samples or urine would be more accessible for individuals.
This study can be found at
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(23)00109-6/fulltext
Paper title
Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study.
Lead Authors
Andrew Siderowf and Claudio Soto.
Publication details including date of publication
This paper was published in The Lancet Neurology in May 2023, article 5, pages 407-417.