Associations between tau PET and CSF MTBR243 do not vary by sex
Bibliographic record
Abstract
BACKGROUND: Prior research, replicated across multiple cohorts, has shown sex differences in tau Positron Emission Tomography (PET), with females exhibiting greater tau tracer binding in medial temporal and neocortical regions, particularly in those with positive amyloid-beta (Aβ) biomarkers. Although typically interpreted as a potentiation of Alzheimer disease (AD) pathology, it remains unclear whether PET methodological factors or underlying biological mechanisms contribute to these observed sex differences. Microtubule binding region tau species containing residue 243 (MTBR-tau243) in cerebrospinal fluid (CSF) is a biomarker of AD tau pathology and has been shown to be associated with tau-PET. However, the potential relationship between MTBR-tau243 and the observed sex differences in tau-PET, remain unexplored. To address this gap, we conducted a cross-sectional analysis of CSF MTBR-tau243 and tau-PET by sex in two cohorts: participants from the Swedish BioFINDER-2 Study and Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight-ADRC). METHOD: Participants were required to have baseline data for both CSF MTBR-tau243 and tau-PET, as well as Aβ status defined by the CSF Aβ42/40 ratio. Tau-PET was measured using the Flortaucipir tracer in the Knight-ADRC cohort and the RO948 tracer in the BioFINDER-2 cohort. In both cohorts, clinical diagnoses were reviewed to identify cases of AD dementia or other dementias. The main analysis of interest was whether there was a significant interaction between sex and CSF MTBR-tau243 in predicting a temporal meta-ROI, with additional analyses examining this interaction in Aβ-positive participants. RESULT: In both cohorts there were significant associations between CSF MTBR-tau243 and the temporal meta-ROI (BioFINDER-2: t = 17.1, p < 0.001, Knight-ADRC: t=11.0, p <0.001). This association was not different by sex (BioFINDER-2: t = 0.54, p = 0.6, Knight-ADRC: t=0.1, p = 0.9) (Figure 1). This finding remained consistent within the Aβ-positive subsets of both cohorts (Figure 2). CONCLUSION: Across two cohorts we found that sex did not moderate the relationship between tau-PET and CSF MTBR-tau243, two distinct markers of aggregated tau pathology. This suggests the sex effects found in tau-PET likely represent a true biological finding not specifically tied to tau-PET methodology.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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) | 0.003 | 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".