Spatiotemporal associations between amyloid and tau pathologies in preclinical Alzheimer’s disease
Bibliographic record
Abstract
BACKGROUND: In Alzheimer's disease (AD), the Thal and Braak staging framework describes the typical regional progression of amyloid-beta (Aβ) and tau, respectively. However, the spatiotemporal relationships between Aβ and tau remain poorly understood. These interactions may influence the rate and pattern of disease progression. We aimed to a) characterize the regional cross-sectional associations between Aβ and tau PET signals, b) examine whether regional Aβ accumulation at baseline predicts subsequent regional tau accumulation over time, and c) examine the regional longitudinal associations between Aβ and tau PET signals. METHOD: We analyzed baseline (n =252) and ∼4.5-year follow-up (n =108) Aβ- and tau-PET scans from cognitively unimpaired individuals with a family history of AD in the PREVENT-AD cohort. Regional SUVRs for Aβ and tau were extracted from 34 bilateral regions of interest using the Desikan-Killiany parcellation. For aim a, region-wise Pearson correlations were computed between baseline Aβ and tau SUVRs. Non-significant correlations were thresholded. Hierarchical clustering identified regional groups with similar Aβ-tau associations. For aim b, the same procedure was used for annual rate of change (aRC). We also assessed baseline Aβ vs tau aRC and vice versa. In both analyses, tau SUVRs or aRC were compared between Aβ- and Aβ+ groups (Centiloid > 20). RESULT: Cross-sectional analyses showed that Aβ SUVRs across most regions were positively correlated with tau SUVRs in the amygdala and medial/inferior temporal lobes. Similar patterns were observed longitudinally. Baseline Aβ in widespread cortical regions was associated with greater tau aRC in the amygdala, precuneus/posterior cingulum, superior-parietal, and lateral occipital cortices. In both analyses, Aβ+ individuals showed higher tau deposition in Braak I and Braak III regions. CONCLUSION: Beyond the inferior/medial temporal lobe regions commonly included in the tau "temporal meta-ROI," we observed significant Aβ associations with both tau and tau aRC in the latero-occipital and superior-parietal cortices. Longitudinal analyses further revealed a strong Aβ-tau relationship in the precuneus/posterior cingulum. As these areas correspond to later Braak stages and are not typically emphasized in early AD assessments, their involvement may reflect spatial tau progression and highlight the need to consider them in future studies of preclinical AD.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".