Inflammation links in Alzheimer’s Disease: connecting fluid proteomics and TSPO PET
Bibliographic record
Abstract
Abstract Background Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer’s disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid‐ β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge. For this reason, the characterization of immune‐related proteins in cerebrospinal fluid (CSF) and plasma would contribute to the understanding of the role of neuroinflammation in the progression of AD. Method Participants from the Translational Biomarker for Aging and Dementia Cohort (TRIAD) incorporating within the AD spectrum, and with available amyloid Aβ ([18F]AZD4694), tau ([18F]MK6240) and TSPO ([11C]PBR28) PET data (positivity = 2.5 SD > mean ROI‐SUVR of young participants), had plasma (n= 151) samples analyzed with the NULISA technology (Alamar Biosciences®). Inflammation‐related proteins (n=72) were selected and included in our analysis, which differential expression was evaluated with linear models (LIMMA) contrasting TSPO groups. After FDR correction for multiple comparisons, the differentially expressed proteins were selected for further analysis, where protein levels were correlated with the PET uptake of 45 anatomical brain regions. Result The differential expression analysis unveiled 5 proteins that are in higher concentrations in the plasma of TSPO positive in comparison with TSPO negative participants (Figure 1): GFAP, CHI3L1, CST3, FABP3, and CHIT1. The correlation analysis between the plasmatic proteins and PET uptake showed significant overlapping correlations with TSPO, Aβ and tau PET in brain regions such as inferior frontal gyrus, inferior occipital gyrus and amygdala (Figure 2). Conclusion These preliminary findings underscore the relevance of GFAP, CHI3L1, CST3, FABP3, and CHIT1 at proxying immune‐related processes in AD, by linking peripherally quantified proteins to brain pathology, as suggested by the colocalized correlations with amyloid, tau and TSPO PET uptake. Further replication of this analysis on the CSF proteomic data of these participants will support the potential significance of these proteins as valuable indicators of neuroinflammation in AD pathology.
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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 | 0.000 | 0.001 |
| 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".