Neuroinflammation potentiates the effect of amyloid‐β on longitudinal tau changes
Bibliographic record
Abstract
Abstract Background It has been proposed that microglia release of proinflammatory factors reactive to amyloid plaques constitutes an early event leading to tau pathology. Here, we assessed how the rate of progression of tau‐PET and the rate of change in plasma pTau217 are affected by baseline levels of amyloid‐β and neuroinflammation. Methods We included 93 individuals from TRIAD cohort: 11 young individuals, 57 cognitively unimpaired elderlies, 15 with mild cognitive impairment and 10 individuals with Alzheimer’s Disease. Neuroinflammation, tau tangle and amyloid‐β (Aβ) deposition were assessed via [ 11 C]PBR28‐PET, [ 18 F]MK6240‐PET and [ 18 F]AZD4694‐PET, respectively. Individuals also had plasma pTau217 quantified using the Alzpath assay. [ 11 C]PBR28‐PET positivity was defined as a SUVR of 2.5SD above the mean of the young individuals in the precuneus and posterior cingulate. Voxel‐based regression models evaluated the interaction of TSPO‐ and Aβ‐PET with annual change in tau‐PET and plasma pTau217. The effect of the interaction on tau‐PET was also evaluated at the region‐of‐interest level using Braak regions. All models were corrected for age, sex and RFT corrected. Comparison of models was made using the Akaike Information Criterion (AIC) and the models’ goodness‐of‐fit was evaluated using R 2 analyses. Models used [ 18 F]MK6240‐PET SUVR yearly change as the outcome and used as predictors [ 11 C]PBR28‐PET SUVR in the precuneus and posterior cingulate and [ 18 F]AZD4694‐PET SUVR in the neocortical region. Results Positive associations were found between the interaction of Aβ‐ and TSPO‐PET at baseline predicting the yearly change in tau‐PET (Figure 1A). At the ROI level, the interaction significantly predicts tau load in Braak regions III‐IV in [ 11 C]PBR28 positive individuals (Figure 1B). Positive associations were also found between the interaction of Aβ‐ and TSPO‐PET at baseline predicting the yearly change in plasma pTau217 (Figure 2A), which is driven by [ 11 C]PBR28 positive individuals (Figure 2B). In addition, the interaction between Aβ‐ and TSPO‐PET predicting the yearly change in tau‐PET is the model with the highest R 2 and the lowest AIC values in Braak regions III‐IV‐V‐VI (Figure 3). Conclusion These results support the hypothesis that microglial activation potentiates the effect of Aβ plaques on tau tangle progression and the pTau217 increases across the aging and AD spectrum.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.002 | 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".