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Organotypic brain slice culture models provide an alternative to early stage  in vivo  studies as an integrated tissue system that can recapitulate key disease features, thereby providing an excellent platform for drug screening. We recently described a novel organotypic 3xTg-AD mouse brain slice culture model with key Alzheimer’s disease-like changes. We now highlight the potential of this model for testing disease-modifying agents and show that results obtained following  in vivo  treatment are replicated in brain slice cultures from 3xTg-AD mice. Moreover, we describe novel effects of the amyloid-binding tetra (ethylene glycol) derivative of benzothiazole aniline, BTA-EG 4 , on tau. BTA-EG 4  significantly reduced tau phosphorylation in the absence of any changes in the amounts of amyloid precursor protein, amyloid-β or synaptic proteins. The reduction in tau phosphorylation was associated with inactivation of the Alzheimer’s disease-relevant major tau kinase, GSK-3. These findings highlight the utility of 3xTg-AD brain slice cultures as a rapid and reliable  in vitro  method for drug screening prior to  in vivo  testing. Furthermore, we demonstrate novel tau-directed effects of BTA-EG 4  that are likely related to the ability of this agent to inactivate GSK-3. Our findings support the further exploration of BTA-EG 4  as a candidate therapeutic for Alzheimer’s disease.

Inhibition of glycogen synthase kinase-3 by BTA-EG4 reduces tau abnormalities in an organotypic brain slice culture model of Alzheimer’s disease