P2‐266: An Effect of I143T PSEN1 Mutation on The Generation of Amyloid B in Culture Cells
Bibliographic record
Abstract
Preseninlin-1 is the catalytic subunit of the γ-secretase complex which cleaves amyloid β precursor protein (βAPP) to form β Amyloid peptide (Aβ). Mutations in Presenilin gene (PSEN1 and PSEN2) have been demonstrated to be the major account for the Early Onset Familial Alzheimer Disease (EOFAD). Recently, both Aβ42 and 43 were reported to be present in plaque cores in the brain of the patients with I143T mutation, which is one of the earliest onset causative genes of EOF AD. (We analyzed an effect of various PSEN mutations on the production of Aβ42 and 43 using culture cells. In order to investigate the effect of PSEN1 mutations on the production of Ap, HEK293 cells stably over-expressing APPswe were transiently transfected with several PSEN1 mutations, and after 24-hour incubation, quantitative change of amount of Aβ40, Aβ42 and Aβ43 in cell culture medium was measured by ELISA. Cells transfected with PSEN1 I143T produced the highest ratio of Aβ42, but the same ratio of Aβ43 to Aβ40, compared with cells transfected with wild type PSEN1, wild type PSEN2, other PSEN1 mutations and PSEN2 mutations. The ratio of Aβ42 to Aβ40, but not of Aβ43, is possibly the important factor for the age at onset of EOF AD I143T, despite the deposition in the brain of the patients mainly consisting of both types of Aβs.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".