THE ABNORMAL PHOSPHORYLATION OF TAU-PROTEIN AT SER-202 IN ALZHEIMER-DISEASE RECAPITULATES PHOSPHORYLATION DURING DEVELOPMENT

Tau is a neuronal phosphoprotein whose expression is developmentally r egulated. A single tau isoform is expressed in fetal human brain but s ix isoforms are expressed in adult brain, with the fetal isoform corre sponding to the shortest of the adult isoforms. Phosphorylation of tau is also developmentally regulated, as fetal tau is phosphorylated at more sites than adult tau. In Alzheimer disease, the six adult tau iso forms become abnormally phosphorylated and form the paired helical fil ament, the major fibrous component of the characteristic neurofibrilla ry lesions. We show here that Ser-202 (in the numbering of the longest human brain tau isoform) is a phosphorylation site that distinguishes fetal from adult tau and we identify it as one of the abnormal phosph orylation sites in Alzheimer disease. The abnormal phosphorylation of tau at Ser-202 in Alzheimer disease thus recapitulates normal phosphor ylation during development.