Hypercholesterolemia accelerates Aβ deposition in regions associated with early amyloidosis
Bibliographic record
Abstract
Abstract Background Hypercholesterolemia is a well‐established risk factor for developing Alzheimer's disease (AD). Mechanisms underlying this relationship, however, are still unclear. Recent experiments have reported conflicting findings regarding the relationship between amyloid‐beta (Aβ) and cholesterol. While in vitro studies have shown that cholesterol accelerates Aβ aggregation, an epidemiological investigation demonstrated that total serum cholesterol is not associated with Aβ load. Nevertheless, it is still unclear whether total serum cholesterol affects Aβ deposition in the human brain. Here, we aimed to assess whether high levels of total serum cholesterol are associated with the rate of Aβ aggregation in the brain. We hypothesized that high total serum cholesterol levels could accelerate cerebral amyloidosis of non‐demented subjects. Method We selected 207 non‐demented – cognitively unimpaired and mild cognitive impairment – participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) who had available data for baseline cholesterol and longitudinal amyloid PET scans with [18F]AV45. Subjects were divided into two groups regarding their total serum cholesterol levels, being classified as normal (<200mg/dL; n=158) or abnormal (>200mg/dL; n=107). We performed a voxel‐wise general linear modelling to assess Aβ load differences between groups at baseline. Then, a longitudinal comparison was carried out to evaluate the rate of Aβ deposition in 4 years, calculated as "(IMAGE4_YEARS ‐ IMAGEBASELINE)x100/IMAGEBASELINE". Age, gender, APOEε4, cholesterol treatment and diagnostic group were used as covariates. Result No differences were found in Aβ load at baseline. By contrast, we observed a significantly higher rate of Aβ accumulation for the abnormal group in brain regions associated to early amyloidosis, including lateral temporal (peak t(200) = 4.498, p<0.0001) and parietal (peak t(200) = 4.504, p<0.0001) lobes, over a 4‐year period when compared to the normal group (Figure 1). Conclusion Our findings suggest that serum cholesterol dysmetabolism could influence cerebral Aβ aggregation. In addition, our analysis points to a potential communication between central and peripheral cholesterol compartments (perhaps intensified by hypercholesterolemia‐related inflammation). Also, it corroborates with the hypothesis that higher serum cholesterol levels accelerate the process of brain amyloidosis, stressing the need for further investigation on the mechanisms involved in this process.
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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 | 0.000 |
| 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) | 0.001 | 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".