MAPT and Alzheimer disease: Despite the fact that the human Tau sequence harbours an amino acid substitution at a key residue within the Tau-2 epitope, it has been proposed that Tau hyperphosphorylation, as seen under pathological conditions such as AD, can alter Tau conformation and restore the Tau-2 epitope, resulting in Tau-2 immunoreactivity with pathological, but not normal, human Tau [85], In our initial testing, Tau-2 failed to detect Tau by WB in any of the samples tested, including human brain protein extracts from tauopathy donors (Supp.