In a recent publication in Aging Cell, Dr. Hong Zhang and collaborators from the University of Massachusetts Chan Medical School and Washington University School of Medicine present their findings in “Elevated p16Ink4a Expression Enhances Tau Phosphorylation in Neurons Differentiated From Human-Induced Pluripotent Stem Cells.”
The study developed a doxycycline-inducible system to control p16Ink4a expression in human iPSCs and their differentiated cortical neurons. Using precise neuronal recordings enabled by NeuroNexus microelectrode arrays, they discovered that upregulating p16Ink4a significantly increases phosphorylation at tau sites (Ser202/Thr205 and Thr231)—an early driver of Alzheimer’s disease pathology—without altering amyloid beta secretion levels.