P1‐190: Acceleration of aging‐dependent changes in adult neural stem cell populations in the 3XTg mouse model of Alzheimer's disease
Bibliographic record
Abstract
Adult neurogenesis, the birth of new neurons within the adult brain is important for cognitive plasticity and continues throughout life in (1) the subgranular zone of the hippocampal dentate gyrus and (2) the subventricular zone (SVZ) of the lateral ventricles. However, this process is down-regulated between early and late adulthood. Several molecules implicated in Alzheimer's Disease (AD), the principal cause of age-related dementia, are potential modulators of adult neurogenesis. We studied neurogenesis in the triple transgenic (3XTg) mouse model of AD, which carries the PS1M146V, APPswe and tauP301L disease-causing human mutations and develops amyloid plaques and neurofibrillary tangles in a progressive and age-dependent manner. We show that genetic mutations associated with AD have early and widespread effects on adult neurogenesis, markedly accelerating aging-dependent changes in neural stem cell activity. In both neurogenic niches of the adult brain, the hippocampus and the forebrain SVZ, there were fewer proliferating cells, progenitors and neuroblasts in middle-aged (11-month-old) and elderly (18-month-old) 3XTg mice compared to age-matched controls. These reductions resulted in fewer newly generated cells in the respective target areas, the dentate granule cell layer and the olfactory bulb. Remarkably, neural precursor activity in the neurogenic areas of middle-aged 3XTg mice was reduced to the levels found in elderly control mice. Cytological examination of the forebrain SVZ further revealed significant local metabolic changes in the 3XTg mice. Moreover, these changes were evident at a relatively early stage of amyloid and tau pathologies, prior to appearance of amyloid plaques or neurofibrillary tangles. Our findings indicate that AD-associated genetic mutations target multiple adult brain neural precursor populations early during the disease process, and suggest that an acceleration of aging-dependent deficits in neural precursor activity may be involved in AD-induced changes in brain structure and function.
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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) | 0.000 | 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 | 0.000 |
| 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 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".