INVESTIGATING BIN1-TAU INTERACTIONS WITHIN PRE-AND POST-SYNAPSES AND THE PROCESSES OF ASTROCYTES IN HUMAN ALZHEIMER’S DISEASE

In Alzheimer’s disease (AD), tau pathology spreads through the brain in a stereotypical pattern through neural circuits. Our previous research demonstrated that oligomeric tau propagates from pre- to post-synapses in mouse models and is present in pre- and post-synaptic pairs in human post-mortem AD brain tissue. This compelling evidence strongly supports trans-synaptic spread as a mechanism of tau propagation in the brain. Additionally, preliminary data suggests the accumulation of synaptic proteins co-localised with pathological tau within astrocytes and microglia in AD brain, implicating glial cells in trans-synaptic tau propagation. Several candidate tau interactors, including BIN1, have been identified in model systems as potential mediators of tau spread, but their roles have yet to be confirmed in the human brain. In this study, we will use tissue embedded for array tomography combined with two high-resolution microscopy techniques: array tomography and Förster resonance energy transfer (FRET), to examine BIN1-tau interactions within pre-and post-synapses and the processes of astrocytes in human AD (n=10) and age and sex-matched control (n=10) brain tissue. These data will aid in identifying specific proteins that pathological tau binds to in the human brain, prompting further research on whether these interactions mediate tau spread.