IC‐01‐02: Effect of APOE‐e4 load and GOLPH2 genotype on regional grey matter volumes in subjects with Alzheimer's disease
Bibliographic record
Abstract
APOEe4 (APOE4) is the best established genetic risk factor for sporadic Alzheimer's disease (AD), and GOLPH2, a Golgi transmembrane protein, has been shown to be a potential susceptibility gene for AD in a recent whole genome scan. In order to better define specific influences of these genes on neurodegeneration, we use a Voxel-Based-Morphometry (VBM) analysis to test for the effects of these genes on grey matter volume (GMV). To determine the genotypic effects of the number of APOEe4 alleles and GOLPH2 (RS10868366) status on regional GMV in AD patients. 100 patients with AD, according to the NINCDS-ADRDA criteria, were recruited for imaging from a larger association genetic study cohort. Satisfactory imaging was available for 83 subjects with APOE genotyping data, and 72 subjects with GOLPH2. In the first analysis, the additive effect of the number of APOE4 alleles was estimated and tested, while in the second the effect of having the GG 'risk' genotype of GOLPH2 (RS10868366) was estimated and tested. In both models, nuisance variables of age, age of onset of AD, gender, image acquisition site, number of years of education and a masking covariate indicating if a manual masking was used to aid the segmentation, were included. An APOE4 additive model showed GMV reduction with increasing APOE4 load in medial temporal lobe structures bilaterally including the amygdala, the hippocampus, the parahippocampal gyrus and the temporal fusiform cortex, as well as in the orbitofrontal cortex, and is shown below in red. Over the significant region, mean GMV was reduced by 13.83±2.53% (mean±SE) in homozygotes compared to non-carriers. The GOLPH2 genotypic model showed GMV reduction in the risk 'GG' genotype in the left frontal pole shown below, with a reduction in GMV of 14.7±2.7% over the significant region. Our analysis identifies a reduction in grey matter volume associated with the number of APOE4 alleles in AD subjects, and to our knowledge is the first formal testing of an additive model for APOE4 effects on localised brain atrophy. We also provide evidence for a regional reduction in grey matter volume associated with GOLPH2 (RS10868366) in AD subjects.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".