Combined Connectomics, <scp><i>MAPT</i></scp> Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease
Bibliographic record
Abstract
Objective We aimed to test whether region‐specific factors, including spatial expression patterns of the tau‐encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity‐based modeling of the spatial variability in tau‐PET deposition in the Alzheimer disease (AD) spectrum. Methods We included 685 participants (395 amyloid‐positive participants within AD spectrum and 290 amyloid‐negative controls) with tau‐PET and amyloid‐PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, 18 F‐AV‐1451‐A05, and BioFINDER‐1). Resting‐state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas. Based on a brain‐parcellation atlas superimposed onto all modalities, we obtained region of interest (ROI)‐to‐ROI functional connectivity, ROI‐level PET values, and MAPT gene expression. In stepwise regression analyses, we tested connectivity, MAPT gene expression, and amyloid‐PET as predictors of group‐averaged and individual tau‐PET ROI values in amyloid‐positive participants. Results Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau‐PET ROI values averaged across amyloid‐positive participants. Stepwise addition of MAPT gene expression and amyloid‐PET increased the proportion of explained variance to 30.2 to 46.0% and 45.0 to 49.9%, respectively. Similarly, for the prediction of patient‐level tau‐PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R 2 range across studies = 0.118–0.148, 0.156–0.196, and 0.251–0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively). Interpretation Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD. ANN NEUROL 2024;95:274–287
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".