ArticleNature communications2024
Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Repositioning of polyubiquitin alters the pathologic tau filament structure.Nature structural & molecular biology · 2026Article
- Beyond structure: spectroscopic imaging in cryogenic electron microscopy.Current opinion in structural biology · 2026Review
- Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center.Science advances · 2026Article
- Cryogenic electron tomography by the numbers: Charting underexplored lineages in structural cell biology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.Cellular and molecular neurobiology · 2026Review
- Visualizing Postsynaptic Density in Excitatory Synapses with Electron Tomography.Advances in neurobiology · 2026Review
- Cryo-EM single-particle analysis expanding towards increasingly native samples.Acta crystallographica. Section D, Structural biology · 2025Review
- Cryoprotectants-assisted plunge freezing of thick brain tissue specimens for targeted physiologically relevant cryo-imagingbioRxiv : the preprint server for biology · 2025Article
- Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A generalizable and targeted molecular biopsy approach for in situ cryogenic electron tomography of vitreous brain tissue.Cell reports methods · 2025Article
- Nanoscale analysis of human G1 and metaphase chromatin in situ.The EMBO journal · 2025Article
- Accurate and fast segmentation of filaments and membranes in micrographs and tomograms with TARDIS.bioRxiv : the preprint server for biology · 2025Article
- Uncovering synaptic and cellular nanoarchitecture of brain tissue via seamlessbioRxiv : the preprint server for biology · 2025Article
- Structural biology inside multicellular specimens using electron cryotomography.Quarterly reviews of biophysics · 2025Review
- Visualizing the virus world inside the cell by cryo-electron tomography.Journal of virology · 2024Review
- Bridging structural biology and clinical research through in-tissue cryo-electron tomography.The EMBO journal · 2024Article
- Serialized on-grid lift-in sectioning for tomography (SOLIST) enables a biopsy at the nanoscale.Nature methods · 2024Article
- Article
- The advent of preventive high-resolution structural histopathology by artificial-intelligence-powered cryogenic electron tomography.Frontiers in molecular biosciences · 2024Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ultrastructure of human brain tissue has traditionally been examined using electron microscopy (EM) following fixation, staining, and sectioning, which limit resolution and introduce artifacts. Alternatively, cryo-electron tomography (cryo-ET) allows higher resolution imaging of unfixed cellular samples while preserving architecture, but it requires samples to be vitreous and thin enough for transmission EM. Due to these requirements, cryo-ET has yet to be employed to investigate unfixed, never previously frozen human brain tissue. Here we present a method for generating lamellae in human brain tissue obtained at time of autopsy that can be imaged via cryo-ET. We vitrify the tissue via plunge-freezing and use xenon plasma focused ion beam (FIB) milling to generate lamellae directly on-grid at variable depth inside the tissue. Lamellae generated in Alzheimer's disease brain tissue reveal intact subcellular structures including components of autophagy and potential pathologic tau fibrils. Furthermore, we reveal intact compact myelin and functional cytoplasmic expansions. These images indicate that plasma FIB milling with cryo-ET may be used to elucidate nanoscale structures within the human brain.
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