Longitudinal welfare assessment in French jump racehorses during season preparation.

Synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and multiple system atrophy (MSA), are associated with the misfolding and aggregation of the protein α-synuclein into toxic insoluble fibrils in the selectively vulnerable regions of the brain. Despite the tangible progress made in our understanding of disease, there's unmet need for establishing reliable and disease-specific biomarkers for diagnosis or progression of synucleinopathies. This need can only be achieved through developing innovative and robust methods and assays for biomarkers discovery and assessments. Various approaches have been employed to detect misfolded α-synuclein aggregates in tissues and biological samples. Among them are antibody-based immunoassays like ELISA, as well as assays that exploit the self-propagating property of α-synuclein aggregates, such as seed amplification assay (SAA). Both approaches have demonstrated notable advantages in the detection and analysis of synucleinopathies in living subjects. Seeding assays, in particular, demonstrate high sensitivity and specificity in detecting α-synuclein aggregates at low levels and even at early stages of the disease, enabling early diagnosis. Several of these studies have shown remarkable specificity scores, effectively discriminating PD, DLB, MSA patients from non-synucleinopathies cases and enhancing our understanding of disease molecular diagnosis. On the other hand, ELISA platforms provide a versatile and widely used approach for quantifying α-synuclein protein levels and/or modified metabolites thereof. Despite their effectiveness, both SAA and ELISA techniques have limitations. SAA despite its sensitivity and promising diagnostic potential lacks direct quantification capabilities, thus meaning it is limited to a binary outcome of positive or negative, and lacking additional data to support stratification of cases for prognostics or clinical trials. Furthermore, SAA kinetic parameters are not always reproducible across cohorts or protocols, which limits their reliability for quantitative interpretation. Prior attempts to relate SAA readouts to clinical measures have relied on kinetic metrics, with mixed reproducibility across studies. These methods necessitate specialized technical expertise and well-equipped laboratories, making them less accessible in routine clinical settings. On the other hand, ELISAs, although widely used, have limited sensitivity in detecting low levels of pathological α-synuclein species in biological samples. Limitations in these techniques, albeit being the most advanced diagnostic techniques currently available, highlight a need for improvements that can allow for a significant advancement in clinical diagnostics of synucleinopathies.