The effect of age on tau burden is dependent on amyloid status in late‐onset Alzheimer's disease
Bibliographic record
Abstract
Abstract Background Growing evidence suggests that middle‐aged subjects with early‐onset AD show higher tau burden and more rapid tau accumulation compared to elderly. Here, we aim to investigate the effects of age, the greatest risk factor in AD, on amyloid, tau, and neuroinflammation in late‐onset AD. We hypothesized the independent effect of age on amyloid and neuroinflammation. However, the effect of age on tau would depend on amyloid load in AD. Method A total of 106 participants (66 A‐T‐, age 20‐86y; 40 A+T‐/A+T+, age 65‐84y) from the TRIAD cohort underwent static 40‐60min 18F‐AZD4694, 90‐110min 18F‐MK620, and 60‐90min 11C‐PBR28 SUVR, as well as MOCA and CDR‐SOB cognitive testing. All images were normalized to the ADNI template, and used cerebellar gray matter as the reference region. The effects of age on amyloid, tau, or neuroinflammation, as well as the interactive effect between age and AT status based on linear regression models. Last, the age‐dependent effect of amyloid, tau, or neuroinflammation on cognition is investigated. All models were corrected for sex, APOE, education, and remaining PET variables. Result We showed a positive main effect of age on amyloid (p<0.001) or neuroinflammation (p=0.05) while no interactive effect between age and AT status was observed. However, a significant interaction between age and AT status on tau in Braakstage1‐2 (p=0.01), Braakstage3‐4 (p=0.001), and Braakstage5‐6 (p=0.002) were observed (Figure1). In relation to cognition, younger subjects with higher tau load performed worse on cognitive testing as shown by a significant negative interaction between age and tau on MOCA. In contrast, age and amyloid showed a positive interactive effect on cognition. Conclusion Our study demonstrated that the age and amyloid or neuroinflammation have a positive association irrespective of the disease status. However, the effect of age on tau deposition depends on the amyloid load such that the presence of pathologic Ab leads to greater tau burden at younger age and worse cognition in late‐onset AD. This supports the framework where tau burden depends on amyloid load following the Ab cascade hypothesis.
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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 | 0.001 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".