Microglial activation and tau propagate jointly across Braak stages
Bibliographic record
Abstract
Abstract Background Compelling experimental evidence suggests that microglial activation is involved in the spread of tau neurofibrillary tangles over the neocortex in Alzheimer’s disease (AD). Here, we tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak‐like pattern in the human brain. Method We studied 130 subjects (86 cognitively unimpaired and 44 cognitively impairment elderly) with microglia activation [11C]PBR28 PET, Amyloid [18F]NAV4694 PET, cognitive tests, magnetic resonance imaging, and cerebrospinal fluid (CSF) biomarkers. Participants also had baseline and follow‐up tau [18F]MK6240 PET scans. We used linear regressions and partial correlations to estimate the association between topographical distributions of microglial activation and tau accumulation. Result (A)Microglial activation (MA) connectivity analysis between regions comprising Braak histopathological stages (Braak I‐VI) across our population demonstrated that MA regions correlated hierarchically with each other, where a Braak‐like stage region only correlates with the previous and subsequent stage. (B)Tau tangles connectivity analysis between regions that comprise Braak stages (Braak I‐VI) across our population demonstrated that tau regions correlated hierarchically with each other, where a Braak stage only correlates with the previous/subsequent stage (C)The scatterplot shows that the elements of the MA‐MA matrix and tau‐tau matrix were highly positively correlated with each other, reinforcing the notion of a joint topographic propagation of MA and tau tangles through Braak stages. (D) Rates of tau propagation over 1‐year hierarchically correlated in Braak stages. (E)Significant Pearson correlation between longitudinal tau propagation and baseline tau network. (F)Significant Pearson correlation between longitudinal tau propagation and baseline microglia network. (G)Partial residuals plots show the results of regression between network of tau propagation over 1‐year and both baseline topographic circuits, MA‐MA and tau‐tau networks. The model suggests that the pathways of longitudinal tau propagation depended on underlying microglia, rather than tau circuits. (H)The figure shows thatmicroglial activation levels in the transentorhinal cortex predicted longitudinal tau spread over the neocortex. Conclusion Our results support a model in which an interaction between amyloid load and activated microglia set the pace for tau spread across Braak stages, while the simultaneous cerebral presence of these pathologies potentiates the development of dementia.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".