P3‐096: THE SYNERGISTIC INTERACTION BETWEEN AMYLOID AND TAU DISRUPTS LOCAL AND GLOBAL RESTING STATE FMRI CONNECTIVITY
Bibliographic record
Abstract
Brain accumulation of beta amyloid plaques (AB) and Tau neurofibrillary tangles are the hallmark of Alzheimer Disease (AD). However, the mechanisms by which they act to cause the clinical manifestation of AD remains unclear. Here we assessed whether the regional interaction of Tau and AB has consequences on both local and global measures of brain functional connectivity. Data from 42 participants (NC = 15, MCI=11, AD=16) recruited from the McGill Centre for Studies in Aging were analysed. Each individual anatomical's T1 image was segmented into 76 cortical and subcortical regions (DKT atlas). Amyloid ([F]AZD4694), Tau ([F]MK6240) PET scan and resting state fMRI sequences were co-registered to the anatomical image. Global [F]AZD4694 and [F]MK6240 SUVR values for each subject were estimated from the frontal, parietal, lateral temporal, and cingulate cortices. The native space pet SUVR was averaged in each regions of the atlas. The atlas-based average of the fractional amplitude of low-frequency fluctuations was used as a proxy for local connectivity and functional connectivity matrices between all pairs of the atlas regions were used to assess global connectivity. Repeated General linear models were calculated for the effect of the interaction of regional Tau and AB on the corresponding regional local connectivity. The interaction of the global Tau and AB load were used for global connectivity. All models were adjusted for age and movement during the rs-fMRI session. When taken separately, the presence of Tau or AB is associated with a reduction of local connectivity in non-overlapping brain regions (Figure 1 b,c). Moreover, the interaction of regional Tau and AB leads to a decrease in local connectivity in AD related areas (Figure 1a). After correcting for multiple comparisons, the interaction of global Tau and AB load is associated with a change of global connectivity for 145 (5%) pairs or regions (Figure 2a). Interestingly, the majority (68%) of these effects are for contralateral connections (upper right quadrant). Global connectivity (gC). The synergistic interaction, rather than the sum of the independent effects of tau and amyloid, leads to the abnormalities in brain connectivity.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 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".