ArticleActa neuropathologica communications2025
Correlative light and electron microscopy imaging of proteinaceous deposits in cell cultures and brain tissues.
Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Future Research Directions on Mycobacterium tuberculosis Proteins.Advances in experimental medicine and biology · 2026Review
- Morphological Changes in Direct Pathway Striatal Neurons in a Rat Model of Tardive Dyskinesia.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Review
- A Step-By-Step Protocol for Correlative Light and Electron Microscopy Imaging of Proteinaceous Deposits in Cultured Cells and Human Brain Tissues.Bio-protocol · 2025Article
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2 authors.
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Abstract
Identifying protein deposits and associated components is crucial for understanding the pathogenesis of neurodegenerative disorders with intracellular or extracellular deposits. Correlative light and electron microscopy (CLEM) has emerged as a powerful tool to accurately study tissue and cellular pathology by examination of the same target at both microstructural and ultrastructural levels. However, the technical challenges with CLEM have limited its application to neuropathology. Here, we developed a simplified efficient CLEM method and applied it to a cell model that produces a high proportion of α-synuclein (αS) inclusions with immunopositivity to phosphorylated αS and the synaptic vesicle marker SV2A and synaptophysin. This approach incorporates modifications in sample processing and innovative fiducial marking techniques, which enhance antigen preservation and improve target registration, respectively. These advancements achieve an optimal balance in sensitivity, accuracy, efficiency, and cost-effectiveness compared to current CLEM methods employing different strategies. Using this method, we identified and analyzed αS inclusions in cell cultures, as well as various pathological protein deposits in postmortem brain tissues from individuals with a range of neurodegenerative disorders. Our findings replicate recently reported new features of αS pathology and also reveal unrecognized a variety forms of small αS inclusions in human brain, which provide valuable insights into mechanisms underlying Lewy-related pathology. Application of this enhanced CLEM method is a powerful tool in research on neurodegenerative disorders, including αS-opathies.
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