P4‐323: Tau phosphorylation links Amyloid beta and NMDA receptor activation, implications for Alzheimer's disease
Bibliographic record
Abstract
Extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles, mainly comprised of phosphorylated tau protein, are the main hallmark of Alzheimer's disease (AD). Mechanistically, it has been suggested that Aß causes alterations in synaptic transmission as well as tau phosphorylation; however the involved intracellular cascade remains largely elusive. To determine whether synaptic activity is related to tau phosphorylation we used rat organotypic hippocampal slice cultures, primary neurons and synaptosomal preparations from rat. We observed that phosphorylated tau protein was present not only in the axon but also in the dendrite and specifically into the spines. Additionally, we found that NMDA receptor activation induces up-regulation of tau phosphorylation at sites Ser199/202, Thr231/Ser235 and Ser396/404 but not at sites Thr212/Ser214. Since it was reported that Aß could affect synaptic NMDA responses, we analyzed the effect of Aß on tau phosphorylation. In this regard, we found that Aß increases tau phoshorylation at sites Thr231/Ser235 and Ser396/404 but not at sites Ser199/202 and Thr212/Ser214 after five days incubation in hippocampal slice cultures. Our results suggest a common pathway between Aß and NMDA receptor activation. Furthermore our data showed that tau phosphorylation caused by NMDA receptor activation is occluded by prior incubation with Aß.
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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) | 0.005 | 0.001 |
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".