Subcellular Injuries in Alzheimer’s Disease
Bibliographic record
Abstract
Alzheimer's disease (AD) is the most common form of dementia occurring in the elderly. Several hypotheses have been proposed to explain the pathophysiology of AD, including amyloidogenesis, disruption of calcium homeostasis, energetic failure, induction of oxidative stress, and hyperphosphorylation of tau protein. This review examines associations between cellular and subcellular injuries, neurodegeneration, and cell death in experimental models, clinical symptoms, and autopsy reports of AD to identify the subcellular events leading to disease onset and progression. The order in which these events occur is discussed. The first injuries reported in AD are subcellular and occur at the Golgi apparatus before any β-amyloid proteins deposit in the Golgi and endosomes. This is followed by lysosomal alterations and the inability of cells to clear β-amyloid. The next stage reveals functional changes and modifications in hippocampal synaptic transmission before structural changes are observed at the cellular level. Subsequently, an extensive intracellular inflammatory process develops in neurons and astrocytes. This inflammatory reaction begins in the nucleus, endoplasmic reticulum, endosomes and mitochondria, and is thought to lead to neurodegeneration and cell death. Finally, the neuroinflammatory response of chronically activated microglia escalates the neurodegeneration and cell death. Identifying the detailed sequence of subcellular events induced by the primum movens defect in AD may lead to the identification of novel drug targets for the treatment of the disease.
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.
How this classification was reachedexpand
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) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 teacher head, 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".