Correlative cryo-soft X-ray tomography reveals defective lysosomes in amyloid-β oligomer treated hippocampal neurons
Bibliographic record
Abstract
Abstract Protein misfolding is common to neurodegenerative diseases (NDs) including Alzheimer’s disease (AD), which is characterized by self-assembly and accumulation of Amyloid-beta in the brain. Furthermore, impaired proteostatic mechanisms have been implicated in NDs. Lysosomes are a critical component of the proteostasis network required to degrade and recycle material from outside and within the cell. Using a model of AD neurodegeneration where toxic amyloid beta oligomers are applied exogenously to primary hippocampal neurons, we have previously established that oligomers are endocytosed and trafficked to lysosomes where they accumulate and prevent further endocytosis. Here, we use pioneering correlative cryo-structured illumination microscopy and cryo-soft X-ray tomography imaging techniques to reconstruct 3D cellular architecture in the native state. We demonstrate that lysosomes in oligomer treated neurons are less X-ray dense suggesting they contain less carbon-rich material than untreated cells. Furthermore, we observe an increase in carbon dense lipid vesicles in oligomer treated cells. This work provides unprecedented and critical visual information on the changes to neuronal architecture inflicted by amyloid beta oligomers using advanced methods in structural cell biology.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".