sTREM2 is associated with attenuated tau aggregate accumulation in the presence of amyloid-β pathology
Bibliographic record
Abstract
Abstract Triggering Receptor Expressed on Myeloid Cell 2 (TREM2) plays a crucial role in the transition of microglia from a state of homeostasis to a state associated with the disease. Mutations in TREM2 are strongly linked with a higher risk of developing neurodegenerative diseases, including Alzheimer’s disease. There have been contradictory findings regarding the potential detrimental or protective effects of microglial activation and TREM2-related microglial responses in Alzheimer’s disease. Although previous studies reported increased CSF soluble TREM2 (sTREM2) in different clinical stages of Alzheimer’s disease, the exact association between Alzheimer’s disease hallmarks such as amyloid-beta and tau pathology remains unclear. In the present study, I aimed to investigate the association between TREM2-related microglial responses and tau accumulation in the presence and absence of amyloid-beta pathology in order to give a better view of the role of microglial activation in Alzheimer’s disease development. Imaging data of 178 non-demented participants including 107 amyloid-beta-negative participants, 71 amyloid-beta-positive were recruited from Alzheimer’s disease Neuroimaging Initiative. The CSF sTREM2 was used as an in vivo indicator of microglial responses associated with TREM2. Furthermore, I used longitudinal tau-PET and resting-state functional MRI connectomes in order to investigate the association of TREM2-related microglial activation and tau spreading through functional connections. A higher level of sTREM2 was associated with slower tau aggregate accumulation in non-demented amyloid-beta-positive. Furthermore, measuring the tau spreading through inter-connected regions using functional MRI connectomes confirms that the TREM2-related microglial activity might be a protective factor against tau pathology in brain tissue. These findings demonstrate that in individuals with initial amyloid-beta abnormalities, TREM2-related microglial activation is linked to reduced regional accumulation of tau aggregates and also, spreading across inter-connected brain regions, as evaluated through functional MRI connectomes during the early stages of Alzheimer’s disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".