P4‐327: SUBTHRESHOLD LEVEL TAU DEPOSITION OCCURS PRIOR TO SUBTHRESHOLD AMYLOID DEPOSITION IN COGNITIVELY NORMAL ELDERLY INDIVIDUALS
Bibliographic record
Abstract
Contrary to the widely accepted hypothesis that amyloid triggers a cascade of events leading to Alzheimer's dementia, histopathological evidence suggests deposition of tau prior to the deposition of amyloid. In this study, we expect to investigate in-vivo evidence of a subthreshold level of tau deposits occurring prior to amyloid deposition using a tau tracer with sub-nanomolar affinity to tangles. For this study, we included 65 cognitively normal elderly individuals from the McGill TRIAD cohort who were scanned with [F]AZD4694 and [F]MK-6240 (standardized uptake value ratios (SUVRs) based on the cerebellum grey matter and inferior cerebellum grey matter as the reference regions respectively). The individuals were categorized into 2 groups based on their amyloid positivity (A-, n=35; A+, n=30). All individuals in the amyloid-negative group were negative for tau as well. For both categorizations, a visual rating was used. Cross-correlation networks (26 cortical ROIs) based on tau and amyloid was generated correcting for age and gender. Bootstrap sampling (n=100) was used to remove any sample bias. A nested stochastic block model analysis was used to identify community structures present in the networks. In the amyloid-negative group (tau-negative), the network analysis did not show any cortical association of amyloid deposition [Fig 1a], whereas tau deposition showed a clear organization [Fig 1b]. Any organization of amyloid deposition was only present in the amyloid-positive group [Fig 1c]. The community analysis indicated the subthreshold tau organization can be represented with 2 communities; one including superior, middle temporal regions, parietal and frontal regions; the other with inferior temporal, parahippocampal cortices, precuneus and cingulate [Fig 1f].
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".