Accelerated rate of plasma <i>p</i> ‐Tau217 progression in amyloid‐β APOE ɛ4 carriers
Bibliographic record
Abstract
BACKGROUND: The ɛ4 allele of the apolipoprotein E gene (APOE) increases susceptibility to Alzheimer's disease (AD) and is associated with reduced responsiveness to amyloid-β (Aβ)-removing therapies. In the context of AD diagnostics and disease-modifying treatments, blood biomarkers have emerged as less invasive, accessible tools for monitoring disease status. This study tested the hypothesis whether APOEɛ4 carriers exhibit differences in plasma phosphorylated tau (p-tau) levels compared to non-carriers, considering the presence/absence of amyloidosis. METHOD: Participants enrolled in the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, Montréal, Canada. Cerebral amyloid-β and tau tangles were assessed using positron emission tomography (PET) imaging with [18F]AZD4694 and [18F]MK6240 tracers. Plasma p-tau217 levels were quantified using commercially available assays (ALZpath and Janssen), while p-tau181 and p-tau231 were measured through in-house Single Molecule Array (Simoa) method. Participants were classified as APOEɛ4 non-carriers (NC) or carriers (C) and further stratified as amyloid-positive (A+) or amyloid-negative (A-) based on PET cut-offs (1.55) or CSF Aβ42/40 ratio (<0.068). Cross-sectional analyses used unpaired FDR-corrected t-tests to compare baseline values between groups. Longitudinal analyses of biomarker progression employed mixed linear effects models. RESULT: 554 participants were included in the cross-sectional analysis (A-NC=260; A-C=92; A+NC=92; A+C=110). At baseline, no significant differences were observed between ɛ4 carriers and non-carriers in plasma p-tau181, p-tau231, and p-tau217 levels in either the A- or A+ groups (Figure 1). Longitudinal data (mean follow-up: 26 months) from 224 participants (A-NC=106; A-C=35; A+NC=37; A+C=46) revealed no significant differences in progression rates for p-tau181 and p-tau231 between carriers and non-carriers, regardless of amyloid status. However, both assays demonstrated accelerated increases in p-tau217 levels among A+ participants (ALZpath: β=0.46, p = 0.02; Janssen: β=0.80, p <0.001), but not in A- individuals (Figure 2). Notably, we detected no significant association between p-tau217 change and the interaction between amyloid beta and APOEɛ4. CONCLUSION: In the presence of amyloidosis, APOEɛ4 carriers accelerate the plasma p-tau217 progression. In contrast, ɛ4 carriership in A+ individuals did not correlate with rates of p-tau181 and p-tau231. An additive interaction between APOEɛ4 carriership and Aβ status was observed. Further investigation is needed to understand the association between APOEɛ4 carriers and AD biomarkers progression.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".