Clusterin is associated with Alzheimer’s disease biomarkers and cognitive scores in the pre‐symptomatic phase of the disease.
Bibliographic record
Abstract
Abstract Background Clusterin (CLU) is one of the main genetic risk factors of late onset Alzheimer’s disease (AD), and different polymorphisms have been associated with the disease. A GWAS performed in a population isolate from eastern Canada has found the polymorphism rs11136000 of the CLU gene to be associated with increased risk for AD. For the present work, we used two different cohorts (the “at‐risk” pre‐symptomatic PREVENT‐AD and the symptomatic ROSMAP cohort) with the objective of exploring how the rs11136000 polymorphism is associated with clinical manifestations, biomarkers and neuropathology of AD at different disease stages. Method In the PREVENT‐AD cohort, ELISAs were used for Tau, phospho(181) Tau (p‐tau), and Aß CSF levels. Cognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Participants were followed for at least 4 years. In the autopsied‐confirmed ROSMAP cohort, Aß load and NFT density in the cortex were measured with immunocytochemistry, and cognition was assessed with the Mini‐Mental State Examination (MMSE). Participants were followed throughout their adult life, until death. Result In the cognitively unimpaired PREVENT‐AD cohort, participants who are APOE4 positive and non‐carriers for the rs11136000 T variant had lower CSF Aß1‐42 (p=0.01) and higher CSF p‐tau (p=0.027) (Fig 1). Additionally, participants who are APOE4 positive and have 2 copies of the CLU rs11136000 T variant display significantly higher coding scores (p=0.003), attention scores (p=0.015) and visuospatial/constructional score (p= 0.026) (Fig 2). However, participants who are APOE4 negative and are homozygous for the rs11136000 T variant have lower semantic fluency score (p=0.001), list recall score (p=0.038) and language score (p=0.007) (fig 2). In the ROSMAP cohort, there was no association of the CLU rs11136000 variant with risk of developing dementia, MMSE scores or Braak or CERAD scores. Conclusion Our results confirm the role of the CLU rs11136000 variant in the pathology of AD, particularly in the pre‐symptomatic phase of the disease when pathology begins to unfold.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".