Pavilion Publishing and Media Ltd
Blue Sky Offices Shoreham, 25 Cecil Pashley Way, Shoreham-by-Sea, West Sussex, BN43 5FF, UNITED KINGDOM
Tel: +44 (0)1273 434 943
Email: [email protected]
Identifying an abnormal build-up of protein deposits on the brain could help to catch Parkinson’s disease early, according to the largest study to date, published in The Lancet Neurology journal.
The study’s findings suggest that the technique – known as Alpha-synuclein seed amplification assays (αSyn-SAAs) – can identify at-risk individuals and those with early, non-motor symptoms prior to diagnosis.
Co-lead author Professor Andrew Siderowf says the study’s findings could have “profound implications” on the way Parkinson’s patients are diagnosed, and could help to identify the best treatments for different subsets of patients, and speed up clinical trials.
As study co-lead author Luis Concha explains: “Our findings suggest that the αSyn-SAA technique is highly accurate at detecting the biomarker for Parkinson’s disease regardless of the clinical features, making it possible to accurately diagnose the disease in patients at early stages.
“Moreover, our results indicate that misfolded α-synuclein is detectable before dopaminergic damage in the brain is about to be observed by imaging, suggesting ubiquitous spread of these misfolded proteins before substantial neuronal damage has occurred.”
How does the test work?
The presence of misfolded α-synuclein protein aggregates in the brain is the pathological hallmark of Parkinson’s disease. The αSyn-SAAs technique can detect these abnormal proteins, and it has long been thought to be a promising diagnostic tool for Parkinson’s disease.
However, while previous research has shown αSyn-SAA can distinguish clearly between individuals with Parkinson’s disease and people without the condition, no large-scale studies have included a broad range of carefully described participants, until now.
The authors of the study assessed the usefulness of αSyn-SAA for identifying underlying heterogeneity in people with Parkinson’s disease, and its ability to detect early signs of the condition.
This included individuals with a diagnosis of Parkinson’s disease, prodromal participants who had non-motor symptoms of Parkinson’s disease but no diagnosis, and at-risk people with gene variants GBA and LRRK2 which are linked to the condition.
The researchers took samples of cerebrospinal fluid that surrounds the brain and spinal cord from each participant and analysed it using αSyn-SAA.
What did the study find?
The study, which involved 1,123 participants, found that αSyn-SAA identifies people with Parkinson’s disease with high accuracy, with positive results in 88% of all participants with a diagnosis.
In sporadic cases – those with no known genetic cause – 93% of individuals had a positive αSyn-SAA result. However, the test was better able to diagnose Parkinson’s disease in people with the GBA variant (96%) compared with the LRRK2 variant (68%).
Certain clinical features of Parkinson’s disease were associated with a positive αSyn-SAA result, including loss of smell (89%) and REM sleep behaviour disorder (85%).
Study author Dr Tanya Simuni notes that α-synuclein pathology may be present even before there is a measurable loss of sense of smell, but more research is needed to confirm this.
She said: “Our study looked at patients at a fixed point in time only, and further research is needed to find out how patients’ sense of smell may change over time, and how this relates to the build-up of a-synuclein aggregates in the brain.”
A “game-changer” in Parkinson’s disease diagnostics, research and treatment
The authors acknowledge some limitations to the study, including that there were low sample numbers for some participant groups and that the data from the Parkinson’s Progression Markers Initiative (PPMI) cohort was collected at a specific point in time.
The availability of PPMI samples collected over time would enable future studies to assess changes over specific time periods, the authors say, and longer-term studies are now needed to further investigate differences in αSyn-SAA results between people with different genetic forms of Parkinson’s disease.
In a linked Comment, Professors Daniela Berg and Christine Klein, of University Hospital Schleswig-Holstein, Germany, say: “Although the blood-based method needs to be further elaborated for scalability, αSyn-SAA is a game-changer in Parkinson’s disease diagnostics, research, and treatment trials.”