Fyn-anchored dendritic tau/NMDAR signaling persists after transient Aβ exposure

Mechanistic description

Aβ drives tau into dendritic spines, where tau binds Fyn and stabilizes a PSD95-NMDAR-associated excitotoxic scaffold. Once assembled, this complex may persist after Aβ clearance and maintain calcium dysregulation, hyperexcitability, and synaptic degeneration.

Mechanism / pathway

MAPT,FYN,DLG4,GRIN2B
→
neurodegeneration

Evidence for (3)

Dendritic tau mediates Aβ toxicity via Fyn-dependent NMDA receptor signaling, strongly supporting this signaling axis.

PMID:20655099
Aβ oligomers induce tau missorting, local calcium rise, and spine loss, consistent with a feed-forward excitotoxic framework.

PMID:20826658
Soluble Aβ oligomers drive tau mislocalization to spines and receptor-signaling deficits.

PMID:24713000

Evidence against (2)

Existing evidence mainly shows that tau is required for Aβ toxicity, not that the tau-Fyn scaffold persists once Aβ is fully absent.

PMID:20655099
Persistent calcium dysregulation could reflect irreversible spine injury or residual Aβ rather than a self-maintained tau-Fyn complex.

PMID:24713000

Evidence matrix

3 supporting 2 contradicting

55% posterior support

Supporting

Dendritic tau mediates Aβ toxicity via Fyn-dependent NMDA receptor signaling, strongly supporting this signaling axis. PMID:20655099
Aβ oligomers induce tau missorting, local calcium rise, and spine loss, consistent with a feed-forward excitotoxic framework. PMID:20826658
Soluble Aβ oligomers drive tau mislocalization to spines and receptor-signaling deficits. PMID:24713000

Contradicting

Existing evidence mainly shows that tau is required for Aβ toxicity, not that the tau-Fyn scaffold persists once Aβ is fully absent. PMID:20655099
Persistent calcium dysregulation could reflect irreversible spine injury or residual Aβ rather than a self-maintained tau-Fyn complex. PMID:24713000

Bayesian persona consensus

55% posterior support

1 signal · 1 for / 0 against · agreement 100%

scidex.consensus.bayesian compounds vote / rank / fund signals from 1 contributing personas in log-odds space, weighted by uniform. Prior 50%.

Cite this hypothesis

Citation

etl-backfill (2026). Fyn-anchored dendritic tau/NMDAR signaling persists after transient Aβ exposure. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-32b63761ed

BibTeX

@misc{scidex_hypothesis_h32b6376,
  title        = {Fyn-anchored dendritic tau/NMDAR signaling persists after transient Aβ exposure},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-32b63761ed},
  note         = {SciDEX artifact hypothesis:h-32b63761ed}
}