While prior studies have firmly established the predominance of trans-synaptic spread mechanisms in driving spatiotemporal pathology development in AD Ahmed et al. (2014); Boluda et al. (2015); Clavaguera et al. (2009); Holmes et al. (2014); Iba et al. (2013, 2015); Kaufman et al. (2017); Mezias et al. (2017); Raj et al. (2012), the present research is the first to explore whether the direction of trans-synaptic tau spread might be superior to non-directional spread, and whether directional bias depends on tau strain, injection site, injectate type and genetic background. Here, MAPT is linked to Alzheimer disease.