APOE ε4 as a predictor of tauopathies independent of β‐amyloid
Bibliographic record
Abstract
Abstract Background Due to the failure of clinical trials that target amyloid β and findings that suggest tau’s role in Alzheimer’s Disease (AD) atrophy and cognitive decline, the investigation of tau‐pathology in AD is needed. While studies have investigated the effect of APOE ε4 on tau‐pathology in mouse models, few have examined the relationship in humans, as well as tau’s role on cognitive decline as a mechanism independent of amyloid β deposition. The aim will be to examine the roles of tau in AD, as an independent pathway. Method Utilizing the National Alzheimer’s Coordinating Center (NACC) database, our sample included those determined with AD, as defined by NACC derived variables. Among participants (n= 5391,Mage= 73, SD=10.5) ε4 carriers accounted for 42%. A separate longitudinal sample (n=108, Mage= 70, SD=9.80) was used to determine cognitive decline as measured by the MoCA. Result The ANCOVA showed a significant effect of APOE carrier status on neurofibrillary tangles after controlling for neuritic plaques, F(1,5390) = 5643.617, p<.001, partial η2=.512 and separately, after controlling for Thal amyloid phases, F(1,2632) =4809.032, p<.001, partial η2=.646. The regression model showed covariates including sex, race, ethnicity, age, education, and language did not contribute significantly to the model, F(6,102) =2.051, p<=0.66 and accounted for 10.8% of the variation on MoCA scores. Introducing APOE carrier status explained 16.5% of the variation of MoCA and was significant in change, F(1,101) =6.891, p=.010. While addition of all neuropathies explained 32.9% of the model, F(3,98) =7.979, p<.001, post hoc T‐tests revealed that only neurofibrillary tangles had a significant effect on cognitive decline, demonstrating a negative relationship. Conclusion These results indicate that the neuropathological effects of APOE ε4 are demonstrated with or without amyloid β deposition, suggesting that apoE may act through tau‐pathways independently. Additionally, while the relationship between APOE ε4 and neuropathology predicts cognitive decline, NFT is the primary driver of cognitive decline in Alzheimer's Disease, while amyloid β deposition has no significant effect.
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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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.004 | 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".