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New York, April 13 – US researchers have developed a breakthrough technique that is a game-changer in identifying the build-up of abnormal protein deposits linked to Parkinson’s disease, an advance that could aid in early diagnosis and may one day also pave the way for treatment.
The findings, published in The Lancet Neurology journal, confirm that the technique — known as Alpha-synuclein seed amplification assay (Alpha Syn-SAA) — can accurately detect people with the neurodegenerative disease and suggest it can identify at-risk individuals and those with early, non-motor symptoms prior to diagnosis.
The presence of misfolded Alpha-synuclein protein aggregates in the brain is the pathological hallmark of Parkinson’s disease.
The study suggests that the AlphaSyn-SAA technique is highly accurate at detecting the biomarker for Parkinson’s regardless of the clinical features, making it possible to accurately diagnose the disease in patients at early stages.
Moreover, the results also indicate that misfolded Alpha-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.
“Identifying an effective biomarker for Parkinson’s disease pathology could have profound implications for the way we treat the condition, potentially making it possible to diagnose people earlier, identify the best treatments for different subsets of patients, and speed up clinical trials,” said Professor Andrew Siderowf, of the University of Pennsylvania Perelman School of Medicine (US).
The technique was assessed among the 1,123 participants with a diagnosis of Parkinson’s disease and at-risk people with gene variants (GBA and LRRK2) linked to the condition.
The study also included prodromal participants — who showed non-motor symptoms like sleep disturbance or loss of smell, which can be early signs of Parkinson’s disease.
Samples of cerebrospinal fluid that surrounds the brain and spinal cord — from each participant were analysed using AlphaSyn-SAA.
Findings of the analyses confirm that AlphaSyn-SAA identifies people with Parkinson’s disease with high accuracy, with positive results in 88 per cent of all participants with a diagnosis (combining sporadic and genetic cases).
In sporadic cases — those with no known genetic cause — 93 per cent of individuals had a positive result. However, it varied for people with genetic forms of Parkinson’s disease, with 96 per cent of those with the GBA variant having a positive AlphaSyn-SAA, compared with 68 per cent of those with LRRK2.
The clinical feature that most strongly predicted a positive AlphaSyn-SAA result was loss of smell — one of the most common symptoms in prodromal people and those with a Parkinson’s disease diagnosis. Among all participants with Parkinson’s disease who had loss of smell, 97 per cent had positive AlphaSyn-SAA compared to 63 per cent of those whose sense of smell was unchanged.
While to harness the full potential of AlphaSyn-SAA, the researchers said blood tests will need to be developed, yet “AlphaSyn-SAA is a game-changer in Parkinson’s disease diagnostics, research, and treatment trials”.