The Effects of an<i>APOE</i>Promoter Polymorphism on Human Cortical Morphology during Nondemented Aging
Bibliographic record
Abstract
Apolipoprotein E (APOE) is the best-known susceptibility gene for AD. It has been well demonstrated that the ε4 allele of the APOE gene can affect brain structure/function in nondemented individuals; however, other polymorphisms in the APOE gene have been largely overlooked when assessing the effects of APOE on the neural system. Rs405509 is a newly recognized AD-related polymorphism located in the APOE promoter region that can regulate the transcriptional activity of the APOE gene. To date, it remains unknown whether and how this APOE promoter polymorphism affects the human brain in aging. Here, for the first time, we investigate the effects of the rs405509 genotype (T/T vs G-allele) on human cortical morphology using a large cohort of nondemented elderly subjects (120 subjects in total; aged 52- 81 years). High-resolution structural MRI was performed; cortical thickness and surface area were analyzed separately. Intriguingly, nondemented carriers of the rs405509 T/T genotype showed an accelerated age-related reduction of thickness in the left parahippocampal gyrus compared with the G-allele carriers. Furthermore, the cortical thickness covariance between the left parahippocampal gyrus and left medial cortex, including the left medial superior frontal gyrus, supplementary motor area, and paracentral lobule, was modulated by the interaction of the rs405509 genotype and age. These novel findings suggest an important role for the APOE promoter polymorphism in the human brain and also provide valuable insights into how the rs405509 genotype shapes the neural system to modulate the risk of developing AD.
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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) | 0.000 | 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) | 0.001 | 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".