Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions
Bibliographic record
Abstract
The e4 allele of the apolipoprotein E gene is the strongest genetic risk factor for sporadic Alzheimer’s disease. Nevertheless, how APOE is regulated is still elusive. In a trans-eQTL analysis, we found a genome-wide significant association between transmembrane protein 106B (TMEM106B) genetic variants and cortical APOE mRNA levels in human brains. The goal of this study is to determine whether TMEM106B is mis-regulated in Alzheimer’s disease or in other neurodegenerative conditions. Available genomic, transcriptomic and proteomic data from human brains were downloaded from the Mayo Clinic Brain Bank and the Religious Orders Study and Memory and Aging Project. An in-house mouse model of the hippocampal deafferentation/reinnervation was achieved via a stereotaxic lesioning surgery to the entorhinal cortex, and mRNA levels were measured using RNAseq technology. In human temporal cortices, the mean TMEM106B expression was significantly higher in Alzheimer’s disease compared to cognitively unimpaired individuals. In the mouse model, hippocampal Tmem106b reached maximum levels during the early phase of reinnervation. These results suggest an active response to tissue damage that is consistent with compensatory synaptic and terminal remodeling.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".