MAPT and Alzheimer disease: Concurrently, we surmise that the identified ApoE4-specific misfolded intermediate state might play a crucial role in the onset of AD by affecting the kinetic of aggregation or the clearance mechanisms of Aβ peptides [19–21] or by promoting the intracellular hyperphosphorylation and consequent self-assembly of tau protein [22,23,52–55].