Technique detects protein accumulation in the brain for early diagnosis of Parkinson’s

A method that identifies the abnormal accumulation in the brain of deposits of a protein, which is associated with Parkinson’s disease, can help in early detection and play a key role in the clinical diagnosis and characterization of the disease, according to research carried out with the group. 1,123 participants, which was published in The Lancet Neurology.

Study results from an American-German team confirm that the technique – known as the α-synuclein amplification assay (αSyn-SAA) – can accurately detect people with the neurodegenerative disease, and suggests it can identify individuals at risk and those with no motor symptoms before diagnosis.

The presence of misfolded α-synuclein protein aggregates in the brain is the hallmark of Parkinson’s disease, the authors note.

Andrew Siderowf, co-senior author, professor of medicine at the University of Pennsylvania (USA) and investigator of the Parkinson’s Progression Markers Initiative (PPMI) indicates that recognizing heterogeneity in disease among patients has been a major study challenge. “Identifying an effective biomarker for Parkinson’s disease could mean improved treatments, earlier diagnosis and accelerated clinical trials”, he points out.

Our results indicate that misfolded alpha-synuclein is detectable before brain damage is imaged.

Luis Concha, co-lead author

“Our findings suggest that the αSyn-SAA technique is highly accurate in detecting the disease biomarker, regardless of clinical features. This makes it possible to accurately diagnose Parkinson’s in its early stages,” insists Luis Concha, also co-lead author and director of R&D at amprion (USA)

In this sense, Concha emphasizes that “the results indicate that misfolded α-synuclein is detectable before brain damage is observable on images, which suggests that the propagation of this protein occurs before substantial neuronal damage.

The new study is the largest analysis of the diagnostic use of αSyn-SAA for Parkinson’s disease with a wide range of carefully described participants, according to the authors.

Detection of early signs

The team evaluated the usefulness of αSyn-SAA in identifying the heterogeneity of people with Parkinson’s and its ability to detect early signs of the disease, using data from the PPMI cohort.

The 1,123 participants in the analysis included individuals diagnosed with the disease and people at risk with genetic variants (GBA and LRRK2) linked to the disease. Also included were so-called prodromal participants, those without motor symptoms but with sleep disturbances or loss of smell, which may be the first signs of the disease. These people had not yet been diagnosed and did not have any of the typical motor symptoms, such as tremors or muscle rigidity, that appear later.

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The researchers note that the reason for including prodromal participants was to determine whether αSyn-SAA could predict the onset of Parkinson’s, as well as help diagnose people with established symptoms.

This method amplifies very small amounts of misfolded α-synuclein aggregates in samples from people with Parkinson’s.

Samples of cerebrospinal fluid – which surrounds the brain and spinal cord – from each participant were analyzed using αSyn-SAA. This innovative method amplifies very small amounts of misfolded α-synuclein aggregates in samples from people with Parkinson’s to the point where they can be detected using standard laboratory techniques, highlights the study.

Positive results in 88% of participants

Analyzes confirmed that this technique identifies people with Parkinson’s disease with high accuracy, with positive results in 88% of all diagnosed participants (combining sporadic and genetic cases).

Autopsy data from 15 participants, all diagnosed with Parkinson’s disease while alive, showed that 14 had typical pathology and were positive for αSyn-SAA.

The study was funded by the Michael J. Fox Foundation and a consortium of more than 40 private partners and charities.

The authors recognize some limitations of the work, which they believe can be improved with a greater number of samples from some groups of participants. They also emphasize that long-term studies would be needed to investigate differences in αSyn-SAA outcomes between people with different genetic forms of Parkinson’s disease.

In a related opinion piece, researchers Daniela Berg and Christine Klein of the University Hospital Schleswig-Holstein in Germany, who were not involved in the study, highlighted the importance of the discovery that αSyn-SAA can detect early signs of the disease.

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research and a consortium of more than 40 private partners and philanthropic entities.

Reference:

Andrew Siderowf, Luis Concha et al. “Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study”. The Lancet Neurology (April 2023).

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