Endolysosome and Autolysosome Dysfunction in Alzheimer’s Disease: Where Intracellular and Extracellular Meet
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Disturbed proteostasis as reflected by a massive accumulation of misfolded protein aggregates is a central feature in Alzheimer's disease. Proteostatic disturbances may be caused by a shift in protein production and clearance. Whereas rare genetic causes of the disease affect the production side, sporadic cases appear to be directed by dysfunction in protein clearance. This review focusses on the involvement of lysosome-mediated clearance. Autophagy is a degradational system where intracellular components are degraded by lysosomal organelles. In addition, "outside-to-inside" trafficking through the endosomes converges with the autolysosomal pathway, thereby bringing together intracellular and extracellular components. Recent findings demonstrate that disturbance in the endo- and autolysosomal pathway induces "inside-to-outside" communication via induction of unconventional secretion, which may bear relevance to the spreading of disease pathology through the brain. The involvement of these pathways in the pathogenesis of the disease is discussed with an outlook to the opportunities it provides for diagnostics as well as therapeutic interventions.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 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) | 0.000 | 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 it