Human nuclear tau and aging

Human tau protein, originally identified as a cytoplasmic protein, binds microtubules with a specific domain. It is codified by the microtubule-associated protein tau gene, which generates six isoforms via alternative splicing of exons 2, 3, and 10. Phosphorylation of 85 different sites (generally serine and threonine residues) determines specific functional properties of the tau isoforms, with hyperphosphorylated tau observed in the neurons of the hippocampus region in the brains of patients with Alzheimer disease. The different isoforms of nuclear tau show various expression patterns in replicative or differentiated cells, and specific epitopes observed in the nucleolus are the phosphorylated AT8 (pSer202/Thr205), AT100 (pThr212/Ser214), and the unphosphorylated Tau-1 (Pro189/Gly207). Recent results indicated the importance of the AT100 epitope as molecular marker of cell aging, and of the AT8/Tau-1 epitopes in neuronal cell differentiation, highlighting a great complexity of tau that goes further to its original function in promoting the assembly of microtubules in neurons.