The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia
Bibliographic record
Abstract
PURPOSE OF REVIEW: We examine current evidence that the transactive response DNA-binding protein (TDP-43) plays a pathogenic role in both amyotrophic lateral sclerosis and frontotemporal dementia. RECENT FINDINGS: TDP-43 was recently identified as the major pathological protein in sporadic amyotrophic lateral sclerosis and in the most common pathological subtype of frontotemporal dementia, frontotemporal lobar degeneration with ubiquitinated inclusions. In these conditions, abnormal C-terminal fragments of TDP-43 are ubiquitinated, hyperphosphorylated and accumulate as cellular inclusions in neurons and glia. Cells with inclusions show absence of the normal nuclear TDP-43 localization. Recently, missense mutations in the gene encoding TDP-43 have been identified in patients with sporadic and familial amyotrophic lateral sclerosis. SUMMARY: The recent discovery of pathological TDP-43 in both amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".