MAPT and Alzheimer disease: Moreover, AD biomarkers (beta-amyloid protein, tau and phosphorylated tau that can be measured in cerebrospinal fluid, plasma or PET) have a relatively low sensitivity to synaptic dysfunction and may be insufficient to monitor modifications of brain function under treatment.6, 7, 8, 9 Furthermore, existing biomarkers do not account for the disjunction between the degree of brain pathology and its clinical manifestations, which refers to the concept of cognitive reserve.10