Microglia as a key player in Aβ‐related astrocyte reactivity
Bibliographic record
Abstract
Abstract Background Glial reactivity has a major role in Alzheimer's disease (AD) etiology and progression, with astrocytes and microglia orchestrating neuroinflammatory responses. Even though experimental evidence indicate that activated microglia can induce astrocyte reactivity, it remains to be elucidated whether microglia activation influences amyloid‐β (Aβ) effects on astrocyte reactivity in the living AD human brain. Using imaging and fluid biomarker data in individuals across the aging and AD clinical spectrum, we tested the hypothesis that microglia influence the effects of Aβ pathology on astrocyte reactivity. Method Data was obtained from the Translational Biomarkers in Aging and Dementia (TRIAD) study. We studied 62 cognitively unimpaired (CU), 26 mild cognitive impairment (MCI), and 13 AD dementia participants who had positron emission tomography (PET) data for TSPO microglial activation ([ 11 C]PBR28) and Aβ plaques ([ 18 F]AZD4694), as well as reactive astrocyte marker plasma glial fibrillary acidic protein (GFAP). We further assessed tau phosphorylation with plasma phosphorylated tau at threonine 217 ( p ‐tau217) and tau aggregation with [ 18 F]MK‐6240 tau tangle PET. Additionally, a subset of 68 CU and 33 MCI individuals from the TRIAD cohort were evaluated with cerebrospinal fluid (CSF) microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2), [ 18 F]AZD4694 Aβ PET, and plasma GFAP. Result Regression analyses revealed that Aβ pathology was associated with astrocyte reactivity only in the presence of elevated levels of microglial activation, supporting that microglial activation influences Aβ effects on astrocyte reactivity. Similar results were observed when using TSPO PET and CSF sTREM2 to assess microglial activation (Figure 1). We also found that microglial activation and astrocyte reactivity were jointly associated with tau phosphorylation and aggregation (Figure 2). Importantly, the microglial‐dependent impact of Aβ on astrocyte reactivity contributed to cognitive impairment through tau pathology (Figure 3). Conclusion Our results suggest that microglial activation is a major phenomenon linking Aβ and astrocyte reactivity in the living AD brain. These findings help to elucidate the intricate crosstalk between microglia and astrocytes in the AD brain, offering insights for the development of glia‐targeting therapies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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 | 0.001 | 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".