Mass spectrometry and genetic screening studies identified synaptogyrin-3 as an interactor of tau, since shown in animal models to enable tau to tether to synaptic vesicles in the terminal space, hindering vesicle release and resulting in presynaptic dysfunction. Pablo Largo-Barrientos, MSc, PhD Student, VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium, discusses recent work aiming to clarify the association between synaptic loss and neuroinflammation in tauopathies, specifically Alzheimer’s disease, and understand the contribution of presynaptic tau to overall tau pathology. Synaptogyrin-3 was knocked out in a tauopathy mouse model (Tau P301S-expressing mice) to determine the effects of lowering its expression. It was shown that knockout of synaptogyrin-3 was sufficient to rescue synaptic loss, cognitive impairment, and electrophysiological defects caused by tau. Neuroinflammation was not affected by synaptogyrin-3 lowering, suggesting tau induces synapse loss and neuroinflammation independently. This interview took place at the AD/PD™ 2022 Conference in Barcelona, Spain.
