Multifractal detrended fluctuation analysis and persistent homology of α-synuclein aggregates across Parkinson's disease stages.

Backgroundα-Synuclein (α-syn) is a prominent protein associated with neurodegenerative conditions such as Parkinson's disease (PD), dementia, and multiple system atrophy, and is a key player in synucleinopathies. Despite its significance, the specific changes in α-syn fibril conformations during the progression of PD remain a subject of uncertainty.ObjectiveThis study investigates the structural alterations in α-syn aggregation from cerebrospinal fluid samples at different PD stages (pre-PD, mid-PD, and late-PD).MethodsIn the present study, we used multifractal detrended fluctuation analysis (MFDFA) and persistent homology. The analysis involves constructing protein contact networks for major and minor α-syn polymorphs. The subsequent application of MFDFA to vertex degree, vertex clustering coefficients, and vertex closeness centrality on this time series data reveals multifractal properties and scaling behaviors. Simultaneously, topological analyses, including Rips complexes, Alpha complexes, and Betti numbers, uncover essential structural features and connectivity patterns in α-syn networks.ResultsThis study illuminates α-syn multifractal dynamics and topological characteristics, providing valuable insights into disease-related protein aggregation and network alterations in the progression of PD.ConclusionsThis study provides unique information on MFDFA and persistent homology of α-syn aggregates across disease stages.