Macrophage Scavenger Receptor 1 in the CSF pre‐symptomatic with a parental history of AD and in the cortex of autopsy‐confirmed Alzheimer’s Disease cases.
Bibliographic record
Abstract
Abstract Background The macrophage scavenger receptor 1 (MSR1) also known as SCARA1, is a gene that encodes for a macrophage/microglia cell surface receptor. Its primary function is to mediate the endocytosis of modified (acetylated or oxidized) low density lipoproteins (LDLs)(Frenkel, Wilkinson et al. 2013). Interestingly, MSR1 has been found to bind to soluble β‐amyloid (Aβ) and it is thought that it participates to its clearance via a microglia‐mediated process (PrabhuDas, Baldwin et al. 2017). Using multiple cohorts covering a wide range of brain health stages, MSR1 gene expression and protein level alterations were investigated to map the associations between MSR1 and Alzheimer’s disease (AD) pathophysiology. Method MSR1 CSF protein levels were assessed in the PREVENT‐AD (PRe‐symptomatic EValuation of Experimental or Novel Treatments for Alzheimer’s Disease) cohort which is composed of subjects with parental history of AD. MSR1 has been measured with a primer extension assay using Olink technology (J. Alz. Dis., In press). ELISA has been used to quantify the MSR1 protein levels in frontal cortex homogenates of 86 brains from the Douglas Bell Canada Brain Bank (DBCBB) whereas MSR1 mRNA prevalence was measured using Gene Chip Clarium D human microarray. All data compilation and statistical analysis has been made using JMP pro 15.1 software. Result Strong correlations between MSR1 CSF protein levels and CSF AD biomarkers, notably phosphorylated Tau (R2=0.108; p=0.0007) and Aβ42 (R2=0.055; p=0.0175) have been found in the PREVENT‐AD cohort. An APOEε4‐independent correlation was observed between CSF MSR1 and APOE (R2=0.156; p˂0.0001) in these cognitively unaffected subjects. In autopsy‐confirmed cortical homogenates, MSR1 protein levels display negative correlations with both Aβ plaques (R2=0.035; p=0.1768) and neurofibrillary tangles (R2=0.136; p=0.0067). On the other hand, MSR1 mRNA levels of the same samples are not correlated with plaques (R2=0.008; p=0.5255) and tangles (R2=0.009; p=0.4971) density. Studies are underway to contrast MSR1 levels with amyloid‐42, p(181)tau and total tau in the same tissues. Conclusion MSR1 plays a significant role in the pathophysiology of AD and recent evidence suggests that elevated MSR1 protein observed in the early stages of AD are followed by a progressive decline that coincides with the emergence of Tau pathology.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".