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Neurodegenerative diseases are common causes of impaired mobility and cognition in the elderly. Among them, tauopathies and α-synucleinopathies were considered. The neurodegenerative processes and relative differential diagnosis were addressed through a qEEG non-linear analytic method. Study aims were to test accuracy of the power law exponent β applied to EEG in differentiating neurodegenerative diseases and to explore differences in neuronal connectivity among different neurodegenerative processes based on β. N = 230 patients with a diagnosis of tauopathy or α-synucleinopathy and at least one artifact-free EEG recording were selected. Periodogram was applied to EEG signal epochs from continuous recordings. Power law exponent β was determined by the slope of the signal power spectrum versus frequency in logarithmic scale. A data-driven clustering based on β values was performed to identify independent subgroups. Data-driven clustering based on β differentiated tauopathies (overall lower β values) from α-synucleinopathies (higher β values) with high sensitivity and specificity. Tauopathies also presented lower values in the correlation coefficients matrix among frontal sites of recording. In conclusion, significant differences in β values were found between tauopathies and α-synucleinopathies. Hence, β is proposed as a possible biomarker of differential diagnosis and neuronal connectivity., (© 2024. The Author(s).)

Equine pituitary pars intermedia dysfunction (PPID) is a common endocrine disease of aged horses that shows a similar pathophysiology as Parkinson's Disease (PD) with increased levels of α-synuclein (α-syn). While α-syn is thought to play a pathogenic role in horses with PPID, it is unclear if α-syn is also misfolded in the pars intermedia and could similarly promote self-aggregation and propagation. Consequently, α-syn was isolated from the pars intermedia from groups of healthy young and aged horses, and aged PPID-afflicted horses. Seeding experiments confirmed the prion-like properties of α-syn isolated from PPID-afflicted horses. Next, detection of α-syn fibrils in pars intermedia via transmission electron microscopy (TEM) was exclusive to PPID-afflicted horses. A bank of fragment peptides was designed to further characterize equine α-syn misfolding. Region 62-87 of equine and human α-syn peptides was found to be most prone to aggregation according to Tango bioinformatic program and kinetics of aggregation via a thioflavin T fluorescence assay. In both species, fragment peptide 62-87 is capable of generating mature fibrils as demonstrated by TEM. The combined animal, bioinformatic, and biophysical studies provide evidence that equine α-syn is misfolded in PPID horses., (© 2021. The Author(s).)