Multimodal <sup>18</sup>F-AV-1451 and MRI Findings in Nonfluent Variant of Primary Progressive Aphasia: Possible Insights on Nodal Propagation of Tau Protein Across the Syntactic Network
Bibliographic record
Abstract
Although abnormally folded tau protein has been found to selfpropagate from neuron to connected neuron, similar propagation through human brain networks has not been fully documented.We studied tau propagation in the left hemispheric syntactic network, which comprises an anterior frontal node and a posterior temporal node connected by the white matter of the left arcuate fasciculus.This network is affected in the nonfluent variant of primary progressive aphasia, a neurodegenerative disorder with tau accumulation.Methods: Eight patients with the nonfluent variant of primary progressive aphasia (age, 67.0 ± 7.4 y; 4 women) and 8 healthy controls (age, 69.6 ± 7.0 y; 4 women) were scanned with 18 F-AV-1451 tau PET to determine tau deposition in the brain and with MRI to determine the fractional anisotropy of the arcuate fasciculus.Normal syntactic network characteristics were confirmed with structural MRI diffusion imaging in our healthy controls and with blood oxygenation level-dependent functional imaging in 35 healthy participants from the Alzheimer Disease Neuroimaging Initiative database.Results: Language scores in patients indicated dysfunction of the anterior node.18 F-AV-1451 deposition was greatest in the 2 nodes of the syntactic network.The left arcuate fasciculus had decreased fractional anisotropy, particularly near the anterior node.Normal MRI structural connectivity from an area similar to the one containing tau in the anterior frontal node projected to an area similar to the one containing tau in the patients in the posterior temporal node.Conclusion: Tau accumulation likely started in the more affected anterior node and, at the disease stage at which we studied these patients, appeared as well in the brain region (in the temporal lobe) spatially separate from but most connected with it.The arcuate fasciculus, connecting both of them, was most severely affected anteriorly, as would correspond to a loss of axons from the anterior node.These findings are suggestive of tau propagation from node to connected node in a natural human brain network and support the idea that neurons that wire together die together.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".