Spatial memory deficits in a mouse model of late-onset Alzheimer’s disease are caused by zinc supplementation and correlate with amyloid-beta levels
Bibliographic record
Abstract
Much of the research in Alzheimer's disease (AD) that uses mouse models focuses on the early-onset form of the disease, which accounts for less than 5% of cases. In contrast, this study used a late-onset AD model to examine the interaction between increased dietary zinc (Zn) and the apolipoprotein E (ApoE) gene. ApoE ε4 is overrepresented in late-onset AD and enhances Zn binding to amyloid-β (Aβ). This study sought to determine if elevated dietary Zn would impair spatial memory in CRND8 mice (CRND8), as well as mice who carry both the mutated human amyloid precursor protein (APP) and ApoE ε4 genes (CRND8/E4). Mice were provided with either lab tap water or water enhanced with 10 ppm Zn (ZnCO3) for 4 months. At 6 months of age, spatial memory was measured by the Barnes maze. CRND8 mice exhibited significant memory deficits compared to WT mice, as shown by an increased latency to reach the escape box. For the CRND8/E4, but not the CRND8 mice, those given Zn water made significantly more errors than those on lab water. During the probe trial for the WT group, those on Zn water spent significantly less time in the target quadrant than those on lab water. These data suggest that increased dietary Zn can significantly impair spatial memory in CRND8/E4. WT mice given Zn water were also impaired on the 24-h probe trial when compared to lab water WTs. Within the CRND8/E4 group only, levels of soluble Aβ were significantly correlated with average primary latencies. Within the Zn-treated CRND8/E4 group, there was a significant correlation between insoluble Aβ and average primary errors. Levels of the zinc transporter 3, ZnT3, were negatively correlated with soluble Aβ (p < 0.01). These findings are particularly relevant because increased intake of dietary supplements, such as Zn, are common in the elderly-a population already at risk for AD. Given the effects observed in the CRND8/E4 mice, ApoE status should be taken into consideration when evaluating the efficacy of therapies targeting metals.
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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".