Direct evidence for dendritic spine compensation and regeneration in Alzheimer's disease models

We developed a targeted optogenetic tool to selectively eliminate individual dendritic spines in live neurons, both in vitro and in vivo. We discovered a two-stage compensatory response to spine loss: rapid enlargement of surviving spines followed by delayed regeneration. We showed that the compensatory enlargement of dendritic spines depends on N-methyl-D-aspartate receptor activation and protein synthesis. We validated across multiple Alzheimer's disease models, demonstrating that similar compensatory plasticity occurs after amyloid beta oligomer-induced synapse loss. We postulate that synaptic resilience is an active neuronal program rather than a passive byproduct of pathology.