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bioRxiv · 10.1101/2025.08.28.672923

Nanoscopic tau aggregates in Parkinson's disease

Layburn, F.·Boken, D.·Zhang, Y.·Halliday, K.·Rodgers, D.·Patel, B.·Quaegebeur, A.·Williams-Gray, C. H.·Klenerman, D.
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Abstract

Post-mortem tau pathology is frequently observed in Parkinsons 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.

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Layburn, F., Boken, D., Zhang, Y., Halliday, K., Rodgers, D., Patel, B., Quaegebeur, A., Williams-Gray, C. H., Klenerman, D.. 2025-09-02. Nanoscopic tau aggregates in Parkinson's disease. https://doi.org/10.1101/2025.08.28.672923

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