An important player is CHIP, an E3 ligase co-chaperone of Hsp90 that can drive the ubiquitination and subsequent proteasomal degradation of tau.126, 127 However, induction levels of CHIP are unchanged in both aged and AD-diseased tissue,42, 94 suggesting that CHIP activity itself cannot be a direct factor in altering the degradation of tau. This evidence concerns the gene MAPT and Alzheimer disease.