Unveiling the synaptic selectivity of tau oligomers: implications for targeted therapeutics in tauopathies

This study provides the first direct evidence of selective synaptic vulnerability to tauO in human brain tissue, revealing a preference for pre-synaptic and inhibitory synapses. These findings challenge post-synaptic-focused therapeutic strategies, such as targeting NMDA and acetylcholine pathways. By identifying pre-synaptic vesicle cycling as a tauO target, our study underscores the need for tau therapeutics tailored to specific synaptic populations and circuits.