Arc Protein Enables Tau Seeding via Extracellular Vesicles in Alzheimer's Mouse Models
Deletion of Arc blocks Tau propagation through extracellular vesicles in Alzheimer's mice but traps toxic aggregates inside neurons, accelerating local cell death. The finding reframes treatment from bulk Tau removal toward interrupting EV-mediated seeding while preserving Arc's protective export function. Evidence remains limited to rodent models with no human validation yet reported.
Future interventions will likely require selective disruption of Tau-Arc binding inside EVs without abolishing Arc's synaptic functions. Human iPSC-derived neuron and cerebral organoid models are the immediate next step to test whether the mouse findings scale before primate or phase-1 safety studies.
Shepherd lab: Selective Arc-Tau interface inhibitors will reduce CSF EV-Tau levels by >40% in non-human primates within 18 months of dosing.
Sources (3)
- [1]Primary Source(https://www.cell.com/cell/fulltext/S0092-8674(26)00630-5)
- [2]Supporting Source(https://www.nature.com/articles/s41586-023-06542-1)
- [3]Supporting Source(https://www.science.org/doi/10.1126/science.abq6836)