Blood Cathepsins on the Risk of Alzheimer's Disease and Related Pathological Biomarkers: Results from Observational Cohort and Mendelian Randomization Study
Bibliographic record
Abstract
BACKGROUND: Alzheimer's disease (AD), the main type of dementia, involves in complex pathophysiological processes, including abnormal lysosomes function. Cathepsins are the predominant proteases responsible for the degradation of diverse substrates in the endo-lysosomal system. However, there was still a lack of systematic study on the causal association between cathepsins and AD. METHODS: This study utilized Mendelian randomization (MR) to investigate the association between blood cathepsins and the risk of AD, as well as the level of amyloid-β (Aβ) and p-Tau in cerebrospinal fluid. Furthermore, an independent dataset was employed to corroborate the above result. Importantly, this study incorporated the Alzheimer's disease Immunization and Microbiota Initiative study Cohort to further validate the alteration of blood cathepsins expression level and examine its correlation with cognitive level and plasma AD-related pathological markers. RESULTS: Using MR method, we observed that high level of cathepsin L (CTSL) was associated with a lower risk of AD in both training and validation data. In observational cohort, we found there was decreased blood CTSL expression level in Aβ+ cognitive impaired (CI) group, compared with Aβ- cognitive unimpaired (CU) group. Correlation analysis revealed that blood CTSL expression level was negatively correlated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) score, plasma Aβ42 and Aβ42/40 level in Aβ+ CI group. Mediation analysis showed that plasma Aβ42/40 level was the key mediator in the association between blood CTSL and MMSE score in Aβ+ CI participants. CONCLUSION: This study revealed that blood CTSL was an important factor affecting the risk of AD, and it affected the cognitive level of AD patients through plasma Aβ42/40 level.
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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 | 0.008 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".