Dynamics of longitudinal biomarker changes in the APP transgenic rat model of AD
Bibliographic record
Abstract
Abstract Introduction: Region-specific neurodegeneration in response to amyloid plaque deposition is a topic of interest of Alzheimer's disease (AD) research. Localization of vulnerable areas can help in understanding underlying pathophysiological processes of the disease. Here, using in-vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging techniques, we assess the longitudinal change in hippocampal volume, as well as structural alterations when correlated with baseline levels of amyloidosis and hypometabolism in McGill-R-Thy1-APP transgenic (Tg) rat model of AD. Methods: In 5 wild-type (Wt) and 9 Tg rats, [18F]FDG-PET and MRI images were collected at baseline (9-11 months) and follow-up (19 months). [18F]NAV4694-PET was collected from 4 WT and 8 Tg rats. First, total intracranial and hippocampal volumes were acquired by manual segmentation method for analysis of changes in the hippocampus. Then, to observe correlation of baseline PET levels with structural MRI changes, seed values obtained from FDG standardized uptake value ratio (SUVr) and NAV binding potential parametric (BPND) images of the frontal cortex, hippocampus, somatosensory cortex and the subiculum at baseline, were correlated with longitudinal deformation maps at voxel-level. Resulting t-maps were Random Field Theory corrected for multiple comparisons. Jacobian values of significant clusters of both Tg and Wt groups were plotted against the baseline PET values, and a linear model of interaction between the PET measurements with the group on the deformation maps refined the clusters. Results: Normalized hippocampal volume showed 8.02% decrease in Tg rats only at follow-up. Amyloidosis at baseline correlated with the shrinkage of the right somatosensory and entorhinal cortices, while hypometabolism revealed shrinkages of the left insular and primary somatosensory cortices, fimbria of the hippocampus, and the hippocampus. Additionally, the expansion of the left lateral ventricle was observed. Discussion: Our results show that amyloid load and hypometabolism at baseline predict spatially distinct structural changes caused by amyloidosis. Moreover, it shows validation of the manual segmentation method when assessing hippocampal volumetry.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".