P4‐179: Young to middle‐aged dogs with high basal Aβ42 CSF level demonstrate learning impairment compared to dogs with low basal CSF Aβ42
Bibliographic record
Abstract
Aged dogs naturally demonstrate several features of Alzheimer's disease (AD) progression including domain-specific cognitive decline and brain pathology, such as amyloid deposition, cerebral atrophy and neuronal loss. Moreover, cerebrospinal fluid (CSF) levels of Aβ42 decrease from middle- to old-age in dogs, and this decrease is inversely correlated with brain amyloid load. Therefore, CSF levels of Aβ may provide a translational endpoint for therapeutic studies. This current study assessed the effect of CSF Aβ42 basal levels in young to middle aged dogs on measures of learning. Twenty young to middle-aged Beagle dogs (2-8 years) were divided into a group demonstrating high (N=10) or low (N=10) basal CSF Aβ42 levels from a larger colony in which basal CSF Aβ42 level was determined as the mean levels from multiple CSF samples collected from the lateral ventricle over several years. The dogs underwent cognitive testing using standardized cognitive tests previously described, including reward approach learning, object approach learning, object discrimination learning and object discrimination reversal learning. Group differences were assessed using independent t-tests. No age differences were noted between the two groups. Similarly, no group differences on reward and object approach were detected. However, the high basal Aβ42 group committed significantly (p<0.01) more errors on the object discrimination learning than the low Aβ42 group. Moreover, subjects in the low Aβ42 group completed reversal learning more rapidly than subjects in the high basal Aβ42 group. Results of ongoing cognitive testing and additional biomarker analysis will be reported. In combination with previous data indicating that no or minimal amyloid plaque deposition is expected in young to middle aged dogs, the current data suggest that high basal Aβ42 CSF level is associated with learning impairments likely prior to amyloid plaque deposition. This finding in the naturalistic canine model of Alzheimer's disease progression warrants the further examination of causal links between high CSF levels of Aβ42 and cognitive impairment prior to amyloid deposition in the progression of AD pathophysiology.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".