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Weakly Supervised Segmentation and Classification of Alpha-Synuclein Aggregates in Brightfield Midbrain Images

2025-11-20 11:51:05
Erwan Dereure, Robin Louiset, Laura Parkkinen, David A Menassa, David Holcman

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder associated with the accumulation of misfolded alpha-synuclein aggregates, forming Lewy bodies and neuritic shape used for pathology diagnostics. Automatic analysis of immunohistochemistry histopathological images with Deep Learning provides a promising tool for better understanding the spatial organization of these aggregates. In this study, we develop an automated image processing pipeline to segment and classify these aggregates in whole-slide images (WSIs) of midbrain tissue from PD and incidental Lewy Body Disease (iLBD) cases based on weakly supervised segmentation, robust to immunohistochemical labelling variability, with a ResNet50 classifier. Our approach allows to differentiate between major aggregate morphologies, including Lewy bodies and neurites with a balanced accuracy of $80\%$. This framework paves the way for large-scale characterization of the spatial distribution and heterogeneity of alpha-synuclein aggregates in brightfield immunohistochemical tissue, and for investigating their poorly understood relationships with surrounding cells such as microglia and astrocytes.

Abstract (translated)

URL

https://arxiv.org/abs/2511.16268

PDF

https://arxiv.org/pdf/2511.16268.pdf


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