Apolipoprotein E ε4 and ε3 alleles associate with cerebrospinal fluid tau and cognition in the presence of amyloid-𝜷 in mild cognitive impairment but not in Alzheimer’s disease
Bibliographic record
Abstract
Apolipoprotein E is the most well-established genetic risk factor for Alzheimer's disease. However, the associations of apolipoprotein E with tau pathology and cognition remain controversial. The research checks the hypothesis that the relationships between apolipoprotein E alleles and cerebrospinal fluid tau and cognition differ in persons with and without significant amyloid-β deposition. We divided 1119 subjects into cognitively normal (n = 275), mild cognitive impairment (n = 629), and Alzheimer's disease (n = 215), and these subjects were from the Alzheimer's Disease Neuroimaging Initiative database. Linear regression models were used to compare the relationships of apolipoprotein E alleles with cerebrospinal fluid tau and cognition in persons with significant amyloid-β deposition relative to individuals without significant amyloid-β deposition. The associations of apolipoprotein E ε4 and ε3 with total tau (T-tau), phosphorylated tau (P-tau), and Alzheimer's disease assessment scale was significantly substantial among participants with significant amyloid-β deposition. Stratified analyses showed that apolipoprotein E ε4 related to increased concentrations of T-tau, P-tau, and Alzheimer's disease assessment scale and apolipoprotein E ε3 associated with decreased concentrations of T-tau, P-tau, and Alzheimer's disease assessment scale in mild cognitive impairment participants with significant amyloid-β deposition, but not in Alzheimer's disease. Our study shows that the presence of apolipoprotein E ε4 and ε3 alleles is related to tau pathology and cognitive impairment in the presence of amyloid-β in mild cognitive impairment, but not in Alzheimer's disease. This work indirectly provides additional evidence that apolipoprotein E and amyloid-β may not have a role in modulating clinical Alzheimer's disease, and apolipoprotein E ε3 may be supposed to be protective to mild cognitive impairment.
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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 | 0.001 |
| 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 | 0.001 |
| 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".