P1‐034: ABCG2 is involved in the transport of beta‐amyloid peptide across the blood‐brain barrier into the brain
Bibliographic record
Abstract
Alzheimer's disease (AD) is characterized by accumulation and deposition of Aβ peptides in the brain. Experimental studies showed that Aβ can be transported across the blood-brain barrier (BBB) into or out-of brain. ABCG2 is an ATP-dependent membrane efflux transporter expressed at the BBB (W. Zhang et al. FASEB J. 17:2085, 2003). We found that ABCG2 is overexpressed in Alzheimer's brain with cerebral amyloid angiopathy (D. Callaghan et al. ICAD2008). This study examines the involvement of ABCG2 in the transport of Aβ1–40 across the BBB. Cloned hABCG2 or empty vector was transfected into HEK293 cells followed by uptake assays with fluorescent dye Cy5.5. Western blot was used to confirm ABCG2 overexpression. Cy5.5 uptake was measured on a microplate reader. Cy5.5-free dye or Cy5.5-labeled Aβ1–40 peptide was intravenously injected into Abcg2 knockout and wild-type mice (Taconic). Mice were scanned alive with a time-domain optical imager eXplore Optix (GE Healthcare Biosciences/ART Inc) at 0, 2, 4, 6, 8 or/and 24h for fluorescent accumulation in the brain. Mice were sacrificed at either 8 or 24h post-injection and ex vivo brains were scanned. Fluorescence in the brain was analyzed for its concentration and intensity. 1) Transient transfection resulted in ABCG2 overexpression in HEK293 cells but not in empty vector-transfected cells. Uptake of Cy5.5-free dye was similar in ABCG2-and empty vector-transfected cells. 2) Equal amount of Cy5.5-free dye was injected into Abcg2KO and wt mice. Concentration analysis showed that Cy5.5 fluorescence was similar in Abcg2KO (average 3.46± SD 0.44) and wt mice (3.44±0.58). 3) Equal amount of Cy5.5-labeled Aβ1–40 was injected into Abcg2KO and wt mice. Concentration analysis showed that Cy5.5 fluorescence was over two-fold higher in Abcg2KO (22.1± 9.47) than wt mice (9.02± 2.52). Fluorescence intensity was over 8-fold higher in Abcg2KO (8.88±0.93) than wt mice (1.03±1.04). 4) Cy5.5-free dye or Cy5.5-labeled Aβ1–40 in equal fluorescent intensity was injected into Abcg2KO mice. Fluorescent concentration was over 6-fold higher in Aβ-injected (24.4±14.2) than Cy5.5-injected mice (3.96±0.66). These results suggest that Cy5.5 is not a substrate of ABCG2 and that Abcg2 is involved in the transport of Aβ1–40 across the BBB into brain.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.005 |
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".