Apolipoprotein E, Not Fibrillar β-Amyloid, Reduces Cerebral Glucose Metabolism in Normal Aging
Bibliographic record
Abstract
The ε4 allele of the polymorphic apolipoprotein E gene is associated with increased risk of Alzheimer's disease (AD), deposition of β-amyloid (Aβ), and reduction in cerebral glucose metabolism in asymptomatic people. Although ApoE4 may exert an effect on AD risk through amyloidogenic pathways, whether its effect on glucose metabolism is related to Aβ is unknown. To answer this question, we examined data from 175 cognitively normal older people (mean age, 77; 87 men, 88 women) in the Alzheimer's disease neuroimaging initiative studied concurrently with [(18)F]flurodeoxyglucose (FDG) positron emission tomography measures of glucose metabolism and the radiotracer [(18)F]florbetapir, an imaging agent which labels fibrillar Aβ in vivo. Based on a threshold value of florbetapir uptake determined in separate samples, subjects were categorized as florbetapir+ or florbetapir-. Glucose metabolism was measured as a continuous variable in a group of regions of interest (ROIs) selected a priori based on their involvement in AD, and also by using a whole-brain voxelwise approach. Among this sample, 29% of subjects were florbetapir+ and 23% were ApoE4 carriers. As expected, there was a significant association between ApoE4 genotype and florbetapir positivity. Florbetapir status, however, was not significantly associated with glucose metabolism, but the ApoE4 genotype was associated with lower metabolism in both voxelwise and ROI approaches. These results show that ApoE genotype, and not aggregated fibrillar forms of Aβ, contributes to reduced glucose metabolism in aging and adds to a growing list of neural consequences of ApoE that do not appear to be related to Aβ.
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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) | 0.000 | 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 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".