synuclein GSKTKEGVVHGVATVA

α-Synuclein (α-syn) is a small protein with an inherent tendency to aggregate and is implicated in several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), collectively referred to as synucleinopathies. Evidence from genetic, pathological, biochemical, and animal model studies strongly supports the role of α-syn aggregation in developing PD and related synucleinopathies. Therefore, developing reliable tools to detect aggregated forms of ?-syn is critical.

Here, we report the creation and characterization of six novel conformation-specific monoclonal antibodies that selectively recognize α-syn aggregates, without binding to its soluble, monomeric form. These antibodies did not recognize monomers or fibrils generated from other amyloidogenic proteins, such as β-syn, γ-syn, β-amyloid, tau, islet amyloid polypeptide, or ABri. Moreover, they did not bind to overlapping linear peptides covering the entire α-syn sequence, confirming their specificity for aggregated α-syn.

In immunohistochemistry, these conformation-specific antibodies revealed previously unappreciated small micro-aggregates and thin neurites in PD and DLB cases, which were not detected by pan antibodies that recognize linear epitopes. Additionally, using one of the antibodies in a sandwich-based ELISA, we detected elevated levels of ?-syn oligomers in brain lysates from DLB cases compared to Alzheimer’s disease and control samples. These conformation-specific antibodies represent valuable tools for research, biomarker development, diagnosis, and potentially immunotherapy for PD and related diseases.

synuclein GSKTKEGVVHGVATVA is a 16-residue synthetic peptide with the sequence Gly-Ser-Lys-Thr-Lys-Glu-Gly-Val-Val-His-Gly-Val-Ala-Thr-Val-Ala. Biotin provides an affinity handle for streptavidin-based capture or detection. These sequence-derived properties describe the reagent chemically; no specific receptor, enzyme, pathway, disease association, or biological activity is assigned without product-specific experimental evidence.

• streptavidin-based capture or detection
• binding and pull-down assay development
• LC-MS/HPLC analytical method development
• sequence-specific assay controls

Sequence-derived chemical properties support reagent selection and experimental planning but do not establish biological function. Solubility, aggregation, adsorption, conjugation efficiency, and assay performance should be validated under the intended experimental conditions.