“…The recent development of tau antibodies that detect PAD exposure (Combs, et al, 2016,Kanaan, et al, 2011) or oligomeric species (Castillo-Carranza, et al, 2014b,Lasagna-Reeves, et al, 2012,Patterson, et al, 2011a,Ward, et al, 2013) has facilitated additional insight into the pathological conformations adopted by tau. More recently, we showed that several disease-related modifications of tau cause conformational display of the PAD in the amino terminus of tau and oligomeric tau aggregates impaired axonal transport confirming a link between pathological conformations and tau toxicity (Kanaan, et al, 2011,LaPointe, et al, 2009,Patterson, et al, 2011a,Patterson, et al, 2011b,Tiernan, et al, 2016). Moreover, many other studies suggest oligomeric tau is toxic to neurons in culture and in vivo (Castillo-Carranza, et al, 2014a,Castillo-Carranza, et al, 2014b,Fa, et al, 2016,Gerson, et al, 2016,Lasagna-Reeves, et al, 2010,Tian, et al, 2013,Usenovic, et al, 2015).…”