AAV9-mediated transduction of memory circuits following convection-enhanced delivery into the olfactory bulbs.

This study explores the potential of adeno-associated virus serotype 9 (AAV9) to deliver therapeutic genes directly into the memory circuit throughout the olfactory bulb (OB), a critical memory and sensory processing region. Using convection-enhanced delivery (CED) of AAV9 encoding green fluorescent protein (GFP), we mapped the extensive neural connectivity from the OB to key memory-related brain regions, including the entorhinal cortex (EC) and hippocampus. Our findings reveal significant transduction of neural pathways and underscore the potential of targeting the OB connectome for therapeutic interventions in progressive neurodegenerative disorders such as Alzheimer's disease or mild cognitive impairment. Targeting the OB connectome will pave the way for new therapeutic strategies to preserve neuronal function and slow the progression, offering a promising avenue beyond symptomatic relief to address the underlying mechanisms of the disease.