Nanoscopic tau aggregates in Parkinson’s disease

Post-mortem tau pathology is frequently observed in Parkinson’s disease (PD) using immunohistochemistry (IHC) to measure large inclusions, however, small protein aggregates that precede inclusions are considered a major driver of toxicity in neurodegenerative disease. We aimed to uncover the distribution of nanoscopic aggregates across six brain regions in post-mortem tissue from 14 PD and 15 controls using the single-molecule pull-down assay (SiMPull). In the hippocampus and amygdala, tau IHC and SiMPull were associated with advanced age in controls and dementia status in PD. Despite negligible tau IHC-labelled aggregates in the putamen, we identified a unique population of high-intensity nanoscopic tau aggregates for a subset of PD cases using SiMPull, ranging from 10–1,000 epitopes per aggregate and 30–1,000 nm in length. Previous evidence linking nigrostriatal tau pathology and motor deficits indicates that the nanoscopic tau aggregates identified in this study may contribute to striatal dysfunction in PD.