A Candidate Regulatory Variant at the TREM Gene Cluster Confer Alzheimer’s Disease Risk by Modulating Both Amyloid-β Pathology and Neuronal Degeneration
Bibliographic record
Abstract
Background: Rs9357347 located at the triggering receptor expressed on myeloid cells (TREM) gene cluster could increase TREM2 and TREM-like transcript 1 (TREML1) brain gene expression, which is considered to play a protective role against Alzheimer’s disease (AD). Objectives: To investigate the role of rs9357347 in AD pathogenesis by exploring the effects of rs9357347 on AD specific biomarkers. Methods: This study analyzed the association of rs9357347 with AD-related cerebrospinal fluid (CSF) and neuroimaging markers from 201 cognitively normal (CN) older adults, 349 elders with mild cognitive impairment (MCI), and 172 elders with AD dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We next analyzed the association in 259 amyloid-β positive (Aβ+) elders and 117 amyloid-β negative (Aβ-) elders (Aβ+: CSF Aβ1-42 ≤ 192pg/ml; Aβ-: CSF Aβ1-42 > 192pg/ml). Associations were tested using multiple linear regression models at baseline. Furthermore, multiple mixed-effects models were used in a longitudinal study which lasted 4 years. Results: At baseline, we found that rs9357347 had association with CSF Aβ1-42 in CN group (β = 0.357, P=0.009). In AD group, rs9357347 was associated with total tau (T-tau) level (β = -0.436, P = 0.007). Moreover, the strong influence exerted by rs9357347 on T-tau was also seen in Aβ+ group (β = -0.202, P = 0.036). In the longitudinal study, rs9357347 was also found to be associated with Aβ1-42 in CN group (β = 0.329, P= 0.023). In AD group, the mutation of rs9357347 was associated with slower accumulation of T-tau (β = -0.472, P = 0.002) and tau phosphorylated at threonine 181 (P-tau 181 [β = -0.330, P = 0.019]). Furthermore, the obvious influence exerted by rs9357347 on T-tau was also seen in Aβ+ group (β = -0.241, P = 0.013). Conclusion: This study suggested that rs9357347 reduced the risk of AD by modulating both amyloid-β pathology and neuronal degeneration.
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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 | 0.000 | 0.001 |
| 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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".