Behavioural and Cognitive Assessment of Aldehyde Dehydrogenase 2 (Aldh2) Null Mice: a New, Oxidative Stress‐Based Model of Age‐Related Alzheimer's Disease (AD)
Bibliographic record
Abstract
The study of AD has been hindered by the absence of animal models of late-onset/age-related AD (95% of AD cases) since current transgenic mouse models exhibit pathological changes dependent on overexpression of mutant human genes linked to early-onset, familial AD (1-5% of cases). Oxidative stress is considered a causative factor in age-related AD, and ALDH2 is important for the catabolism of toxic aldehydes (eg. 4-hydroxynonenal, HNE) associated with oxidative stress-induced lipid peroxidation. Aldh2 null mice exhibit oxidative stress, many AD-like pathologies, and importantly, age-related decreases in performance in recognition and spatial memory tasks beginning at 3 months of age and maximal at 6 months. Differences in locomotor activity and coordination, as well as behavioural phenotype using the open field test, balance beam and SHIRPA standardised battery were not observed, suggesting that diminished cognitive performance was the result of impaired memory and not due to confounding changes in motor function. Additionally, chronic administration of GT1061, a neuroprotectant that targets synaptic failure via activation of NO/cGMP/pCREB signaling, and histidine hydrazide, an HNE scavenger, reverses the progressive memory deficits and biochemical changes that occur in these mice. The presence of AD-like pathologies and the reversal of memory and biochemical deficits by pharmacological intervention, suggests that Aldh2 null mice represent a new, oxidative stress-based model of age-related cognitive impairment and AD that may prove useful both for assessing AD therapeutics and for gaining better insight into the pathogenesis of AD.
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 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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".