Misfolded alpha-synuclein in amyotrophic lateral sclerosis: Implications for diagnosis and treatment.

Background: Alpha-synuclein (α-Syn) oligomers and fibrils have been shown to augment the aggregation of TAR DNA-binding Protein 43 (TDP-43) monomers in vitro, supporting the idea that TDP-43 proteinopathies such as ALS may be modulated by the presence of toxic forms of α-Syn. Recently, parkinsonian features were reported in a study of European patients and Lewy bodies have been demonstrated pathologically in a similar series of patients. Based on these and other considerations, we sought to determine whether seed-competent α-Syn can be identified in spinal fluid of patients with ALS including familial, sporadic, and Guamanian forms of the disease.

Seed amplification assay results illustrate discrepancy in Parkinson's disease clinical diagnostic accuracy and error rates.

Parkinson's disease (PD) may be misdiagnosed due to the clinical overlap between PD and atypical parkinsonism. The utility of α-Synuclein (αSyn) Seed Amplification Assay (SAA) as a diagnostic indicator for PD has been reported in numerous studies, but never when administered as a validated clinical laboratory test. This study compares results from αSyn-SAA validation testing performed using well-characterized cohorts from two biorepositories to better understand the accuracy of PD clinical diagnosis.