KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease
Bibliographic record
Abstract
Abstract Klotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShetis associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShetand levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShetshowed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VSheton tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VShetwas related to better memory functions in amyloid-positive participants and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VShetcarriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VShetagainst amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.
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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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".