Laminar distribution of the pathological changes in sporadic frontotemporal lobar degeneration with transactive response (TAR) DNA‐binding protein of 43 kDa (TDP‐43) proteinopathy: a quantitative study using polynomial curve fitting
Bibliographic record
Abstract
R. A. Armstrong, R. L. Hamilton, I. R. A. Mackenzie, J. Hedreen and N. J. Cairns (2013) Neuropathology and Applied Neurobiology 39, 335–347 Laminar distribution of the pathological changes in sporadic frontotemporal lobar degeneration with transactive response (TAR) DNA‐binding protein of 43 kDa (TDP‐43) proteinopathy: a quantitative study using polynomial curve fitting Aims: Previous data suggest heterogeneity in laminar distribution of the pathology in the molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA‐binding protein of 43 kDa (TDP‐43) proteinopathy (FTLD‐TDP). To study this heterogeneity, we quantified the changes in density across the cortical laminae of neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe. Methods: Changes in density of histological features across cortical gyri were studied in 10 sporadic cases of FTLD‐TDP using quantitative methods and polynomial curve fitting. Results: Our data suggest that laminar neuropathology in sporadic FTLD‐TDP is highly variable. Most commonly, neuronal cytoplasmic inclusions, dystrophic neurites and vacuolation were abundant in the upper laminae and glial inclusions, neuronal intranuclear inclusions, abnormally enlarged neurones, and glial cell nuclei in the lower laminae. TDP‐43‐immunoreactive inclusions affected more of the cortical profile in longer duration cases; their distribution varied with disease subtype, but was unrelated to Braak tangle score. Different TDP‐43‐immunoreactive inclusions were not spatially correlated. Conclusions: Laminar distribution of pathological features in 10 sporadic cases of FTLD‐TDP is heterogeneous and may be accounted for, in part, by disease subtype and disease duration. In addition, the feedforward and feedback cortico‐cortical connections may be compromised in FTLD‐TDP.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".