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.
Evidence for (3)
Dendritic tau mediates Aβ toxicity via Fyn-dependent NMDA receptor signaling, strongly supporting this signaling axis.
Aβ oligomers induce tau missorting, local calcium rise, and spine loss, consistent with a feed-forward excitotoxic framework.
Soluble Aβ oligomers drive tau mislocalization to spines and receptor-signaling deficits.
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.
Persistent calcium dysregulation could reflect irreversible spine injury or residual Aβ rather than a self-maintained tau-Fyn complex.
Bayesian persona consensus
scidex.consensus.bayesian compounds vote / rank / fund
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