Hallmark Parkinson's Disease Protein May Aid Early Detection

A technique known as α-synuclein seed and amplification assay (αSyn-SAA) that identifies the presence of misfolded α-synuclein protein aggregates in the brain could help in the early diagnosis of Parkinsons disease. This finding is according to a new study published in the Lancet Neurology journal. Historically, biochemical tests could not provide a conclusive diagnosis during life -- therefore, the disease has previously been defined based on clinical symptoms and post-mortem brain pathology.

Importance of Identifying an Effective Biomarker for Parkinson’s Disease

α-synuclein seed amplification assay (αSyn-SAA) technique amplifies very small amounts of misfolded α-synuclein aggregates in samples from Parkinson’s patients so that they can be detected using standard laboratory techniques. The researchers sought to assess αSyn-SAA’s usefulness in detecting early signs of Parkinson’s.

Researchers used data from the Parkinson’s Progression Markers Initiative cohort. Among the 1,123 participants were individuals with a Parkinson’s disease diagnosis, and at-risk people with gene variants linked to the condition. Samples of participants’ cerebrospinal fluid, which surrounds the brain and spinal cord, were analyzed using αSyn-SAA.

Prodromal individuals exhibit non-motor symptoms, including REM sleep disturbance and loss of smell -- both potential Parkinson’s precursors -- but lack the tremors or muscle stiffness that come later in the disease’s development. Prodromal participants were included to help determine αSyn-SAA’s usefulness in predicting Parkinson’s onset.

αSyn-SAA : A Useful Technique for Diagnosing Parkinson’s Disease

Findings confirmed that αSyn-SAA can accurately detect people with Parkinson’s disease, with positive results in 88% of diagnosed participants. Most prodromal participants had positive αSyn-SAA results, indicating α-synuclein aggregates, despite not having been diagnosed with Parkinson’s disease.

Among those recruited with the sleep disorder, 85% had positive αSyn-SAA results. Similarly, among those reporting the loss of smell, 89% had positive αSyn-SAA results. Such loss of smell was the clinical feature that most strongly predicted a positive αSyn-SAA result.

Among participants with Parkinson’s disease and loss of smell, 97% had positive αSyn-SAA results compared to 63% of those whose sense of smell was unchanged.

Importantly, most prodromal participants with positive αSyn-SAA results had brain scans that did not show a decline in the number of dopamine-producing nerve cells, a pre-diagnosis biomarker. The loss of dopamine-producing cells has been implicated as a cause of Parkinson’s disease.

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This result suggests that misfolded α-synuclein buildup may be a very early indicator of disease onset. That the detection of α-synuclein before brain damage is observable by imaging suggests the ubiquitous spread of these proteins before substantial neuronal damage.

These 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 at its early stages.

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Source-Eurekalert