Neuronal Extracellular Vesicles Carrying APOE Downregulate Filament Actin Polymerization Signaling to Inhibit Synapse Formation in Alzheimer's Disease - PubMed
3 days ago
- #Alzheimer's disease
- #Synapse formation
- #Extracellular vesicles
- Neuronal extracellular vesicles (EVs) from APP/PS1 mice (APPNEVs) impair synapse formation in Alzheimer's disease (AD).
- APPNEVs downregulate synaptic proteins PSD95 and Synaptophysin (SYP), reducing synapse number and maturity.
- Proteomic analysis identifies APOE as a key upregulated protein in APPNEVs.
- Pharmacological inhibition of APOE with EZ-482 prevents APPNEV-induced synaptic damage.
- APPNEVs suppress Rac1-N-WASP-Arp2/3-mediated filament actin polymerization, critical for synaptic spine formation.
- In vivo studies confirm APPNEVs' detrimental effects on synaptic integrity, reversible with APOE inhibition.
- Findings highlight APOE as a potential therapeutic target for preserving synaptic formation in AD.