SCARF2 in the CSF of Asymptomatic subjects With a Parental History of AD and in the Cortex of Autopsy‐Confirmed Alzheimer’s Disease Cases
Bibliographic record
Abstract
Abstract Background Scavenger receptors (SR) are a group of receptors involved in the endocytosis of various ligands, such as modified LDL and soluble β‐amyloid, which connects them to Alzheimer’s disease (AD). SCARF2 (SREC‐II) is part of the SR family, but unlike other scavenger receptors, internalizes a low amount of modified LDL. Its main function revolves around the binding of Aβ (Vo et al. 2023). Other studies found SCARF2 to be a SCARF1 inhibitor (Ishii et al. 2002). This study compares gene expression and protein levels of SCARF2 in post‐mortem brain tissue of AD and control subjects, as well as in the CSF of participants with a family history of AD. The goal is to track the progression of AD using the expression pattern of SCARF2. Method SCARF2 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 asymptomatic subjects with parental history of AD. SCARF2 has been measured with a primer extension assay using Olink technology. ELISA immunoassay has been used to quantify SCARF2 protein levels in frontal cortex homogenates of 86 brains from the Douglas Bell Canada Brain Bank (DBCBB). mRNA prevalence was measured using Gene Chip Clariom D human microarray. All statistical analyses were performed using JMP pro 17 software. Result SCARF2 Protein levels, but not mRNA, are significantly lower in brains with AD (p<0.001). SCARF2 protein display a strong negative association with plaques bound Aβ, despite being a well‐established Aβ receptor (R2 = 0.277, p<0.0001). Interestingly, CSF protein levels correlate positively with AD biomarkers such as total and phosphorylated(181) tau (R2 = 0.235, p<0.0001; R2 = 0.288, p<0.0001) and Aβ to a lesser extent (R2 = 0.045, p = 0.0318). Conclusion Our study unveils a distinctive role for SCARF2 in AD pathogenesis. Despite being a known Aβ receptor, SCARF2 exhibits lower cortical protein levels in AD brains, inversely linked to plaques bound Aβ. In contrast, elevated CSF SCARF2 protein levels correlate positively with CSF AD biomarkers in the presymptomatic phase of the disease; suggesting differential response to amyloid and tau deposition. These findings shed light on the intricate interplay of SCARF2 in AD pathophysiology, offering potential avenues for further research.
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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".