MAPT and Alzheimer disease: Tau hyperphosphorylation not always leads to aggregation but rather seems to play a dual role in the brain.33 Phosphorylation sites like serine-262 have been widely studied in the context of brain development and more recently recognized as a critical epitope involved in tau pathology and tangle formation in Alzheimer’s disease,9,11 suggesting shared mechanisms in brain physiology and pathology.