Association of reactive astrogliosis and microglial activation with tau pathology in Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Glial contributions to Alzheimer’s disease (AD) etiology and progression have been increasingly recognized. Experimental and clinical evidence suggests that both microglial activation and astrocyte reactivity have pivotal roles in the progression of tau pathology. However, it remains to be elucidated how microglia and astrocytes complement each other in AD pathogenesis. Here, we tested the associations between reactive astrogliosis and microglial activation with tau phosphorylation and aggregation in individuals across the aging and AD spectrum. Method We studied 95 participants (14 cognitively unimpaired [CU] young, 46 CU elderly, and 35 cognitively impaired [CI]) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. Individuals had available positron emission tomography (PET) for Aβ ([18F]AZD4694), tau tangles ([18F]MK6240), and microglial activation ([11C]PBR28). We further assessed reactive astrogliosis (plasma glial fibrillary acidic protein [GFAP]) and pathological tau phosphorylation (plasma phosphorylated tau [p‐tau] at threonine 231, 181, and 217). Result Demographic characteristics of the study population are reported in Table 1. Regression analyses revealed that reactive astrogliosis and microglial activation were synergistically associated with higher plasma phosphorylated tau levels independently of Aβ pathology in CU but not CI individuals (Figure 1A). On the other hand, no interactive effects of reactive astrogliosis and microglial activation on tau‐PET burden were observed in either CU or CI individuals (Figure 1B). Similar findings were observed in sensitivity analyses excluding CU young participants. Conclusion Our results suggest that reactive astrocytes and activated microglia have Aβ‐independent synergistic effects on the early progression of AD pathophysiology by contributing to tau phosphorylation but not tau aggregation. These findings can help to better understand the complementary roles of glial cells in neurodegenerative diseases, as well as provide insights for the development novel therapeutic strategies for AD targeting the interplay between astrocyte and microglial reactivity.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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".