P1‐330: Simple <i>in vitro</i> screening assays for agents that inhibit beta‐amyloid deposition or promote beta‐amyloid phagocytosis
Bibliographic record
Abstract
A-beta deposits powerfully stimulate inflammation in AD brain. Agents that inhibit the buildup of these deposits, or assist in their phagocytosis should be effective therapeutic agents. We developed simple in vitro screening assays to identify such agents as a preliminary to in vivo testing. Inhibition of beta-amyloid aggregation. For details see J-P Guo et al., JAD 19; 2010. Test agents were mixed with a fluorophore labeled beta-amyloid 42 probe for 30 minutes at 37C. The mixture was then applied in the dark to plaque containing AD brain sections for one hour at room temperature. Binding of the A-beta fluorophore to A-beta deposits was observed microscopically. Inhibition of test agents was assessed quantitatively. Enhancement of phagocytosis. Uptake of FluoSphere beads (diameter 0.02um) by THP1 cells was assessed. Test agents and 1ul of 0.025% microsphere beads were added into wells containing 2X10 4 THP1 cells in 200ul of HBSS. The mixture was incubated in the dark for one hour at 37C. After washing with HBSS, the cells were smeared on glass slides, air-dried and fixed in methanol/acetone (1:1). The fluoro-phagocytosis signal was observed microscopically and enhancement of phagocytosis determined semi-quantitatively. For beta-amyloid phagocytosis, 1ul of 0.1mg/ml beta-amyloid-HiLyte488 probe and test agents were similarly added to wells and incubated for one hour at 37C. The cells were treated and observed as the described previously. Several thousand medicinal agents were tested for their ability to inhibit beta amyloid binding and several hundred for enhancing its phagocytosis by THP-1 cells. Some highlights were that 1mg/ml of 1,2,3,4,6-penta-O-galloyl-b-D-glucopyranose (PGG) completely blocked fluoro-beta-amyloid probe binding while 0.5ug/ml enhanced phagocytosis . 1mg/ml of resveratrol partially blocked fluoro-beta-amyloid probe binding while 50ug/ml enhanced phagocytosis. 5mg/ml of (-)-borneol almost completely blocked fluoro-beta-amyloid probe binding while 25ng/ml enhanced phagocytosis. 0.5mg/ml of epigallocatechin gallate (EGCG) almost completely blocked fluoro-beta-amyloid binding, but even at 50ug/ml it had no effect on phagocytosis. 0.5% ginger extract completely blocked fluoro-beta-amyloid binding but 2.5% completely blocked phagocytosis. PGG, resveratrol and borneol are attractive agents for in vivo testing because they can hinder beta-amyloid deposition while enhancing its phagocytosis by THP1 cells.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.004 |
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".