Four studies with important data regarding the biggest challenges of seed amplification assays (SAAs), a biomarker that could aid in early diagnosis and disease differentiation for Parkinson's disease, were released today at the International Congress of Parkinson's Disease and Movement Disorders® in Philadelphia.
PHILADELPHIA, Sept. 27, 2024 /PRNewswire-PRWeb/ -- Four studies with important data regarding the biggest challenges of seed amplification assays (SAAs), a biomarker that could aid in early diagnosis and disease differentiation for Parkinson's disease, were released today at the International Congress of Parkinson's Disease and Movement Disorders® in Philadelphia.
Alpha-synuclein (α-Syn) SAAs have been shown to successfully detect synucleinopathies, neurodegenerative conditions with abnormal aggregated α-syn protein in neurons, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, α-syn SAAs have faced challenges with differentiating between synucleinopathy diseases, quantifying α-syn beyond a binary presence or absence, and accessibility of the tissue sample for biomarker testing.
Testing single vs multiple proteins
The first study from Weber and colleagues examined the proportion of positive α-syn SAA tests in a large cohort with neurodegenerative diseases including tauopathies (31.3% positive α-syn SAA), Alzheimer's disease (38.1%), vascular PD (25.5%) and idiopathic normal pressure hydrocephalus (27.5%). This study highlights the complexity of underlying proteinopathies and that most syndromes are not caused by a single protein.
By leveraging the presence of multiple proteins, the second study by Jabbari et al. introduces a promising disease differentiation technique with the combination α-syn and 4-repeat tau (4RT) SAA. This technique provides a potential solution to challenging diagnosis and clinical overlap between synucleinopathies, such as PD and multiple system atrophy (MSA), and that of tauopathies, such as progressive supranuclear palsy (PSP) and corticobasal degeneration.
"The reported results are exciting, since they take a biomarker-based approach in the differential diagnosis between the 4R-tauopath PSP and the alpha-synucleinopathy PD, relying on SAAs for tau and α-syn, respectively," said Gunter Höglinger, head of the neurology department at the Ludwig-Maximilians-University in Munich.
"The currently reported data of 7.7% of clinically diagnosed PSP patients being positive for synuclein SAA are in line with the prevalence of synuclein copathology previously observed in autopsy series of PSP patients, but surprisingly the 2 autopsy-confirmed PSP patients, which were actually synuclein SAA-positive in the current series, did not have Lewy body copathology at postmortem examination," he said. "This finding opens up many questions regarding the sensitivity and specificity of the SAA versus immunohistology. Tau SAA is a more recent development with very limited published experience. The authors report Tau SAA positivity in all 6 PSP brain samples examined, providing initial evidence of feasibility and good sensitivity of the assay; however, further work will need to establish specificity and the feasibility in peripheral tissues and blood, validated against the ground truth of histopathology."
Improvements in diagnostic assay technology
A study by El-Agnaf and colleagues introduces a novel diagnostic assay, named Seeding Amplification ImmunoAssay (SAIA), capable of quantifying minute amounts of α-syn fibrils, demonstrating diagnostic efficacy. Furthermore, this assay is capable of distinguishing synucleinopathies, such as PD, MSA and DLB, from non-synucleinopathies with sensitivities and specificities ranging from 80% to 100%.
"The study highlights the key role of SAIA in detecting early synucleinopathies, both at clinical and prodromal stages," said Margherita Fabbri, neurologist at the Toulouse University Hospital. "This represents an invaluable tool for patient selection in clinical trials. Notably, a relationship between cerebral spinal fluid α-syn seeds and disease severity is demonstrated, paving the way for SAIA to be used as a biomarker of disease stage. Further exploration of SAIA's value as a biomarker in longitudinal studies and a clearer definition of its role at the prodromal stage are crucial points for future research."
The fourth α-syn quantifying study by Bellaire et al. implements a digital pathology detection tool to measure phosphorylated α-syn (P-SYN) within cutaneous axons. Biopsies from patients with PD, MSA, or DLB were collected from three body regions and measured via confocal microscope and AI-driven quantification.
"The study is innovative as it utilizes artificial intelligence-driven quantitation of nerve fibres and intra-axonal P-SYN," said Diana A. Olszewska, Cork University Hospital in Ireland. "The skin holds unapparelled potential to serve as easily accessible tissue for the perfect biomarker.
"The quantitative data presented in the study can differentiate alpha-synucleinopathies from controls, although not between DLB and MSA — where the standard deviation overlapped. However, when combined with different topographical patterns of P-SYN deposition described in each condition, it may allow for differentiation between PD, DLB, and MSA. The study paves the way for further research to examine the potential for the described method to monitor quantitative differences in P-SYN deposition as they evolve. This holds significant implications for developing a biomarker for diagnosis and future disease monitoring to ensure the success of disease-modifying trials."
These four studies represent important advancements that could make α-syn SAA biomarkers used more broadly.
Full text of these abstract are be available at mdsabstracts.org (Reference #s: 59, 123) or mdscongress.org/IC24-late-breaking-abstracts.pdf (Reference #s: LBA-2, LBA-3).
About the 2024 MDS International Congress of Parkinson's Disease and Movement Disorders®:
The MDS International Congress is the premier annual event to advance the clinical and scientific discipline of Movement Disorders, including Parkinson's disease. Convening thousands of leading clinicians, scientists and other health professionals from around the globe, the International Congress will introduce more than 1,800 scientific abstracts and provide a forum for education and collaboration on latest research findings and state-of-the-art treatment options. Learn more at http://www.mdscongress.org.
About the International Parkinson and Movement Disorder Society:
The International Parkinson and Movement Disorder Society® (MDS), an international society of more than 11,000 clinicians, scientists, and other healthcare professionals, is dedicated to improving patient care through education and research. For more information about MDS, visit http://www.movementdisorders.org.
Media Contact
Shea Higgins, International Parkinson and Movement Disorder Society, +1 (414) 276-2145, [email protected], movemetndisorders.org
SOURCE International Parkinson and Movement Disorder Society
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