Cystatin C (CysC) is a cysteine protease inhibitor of cathepsin family, lysosomal proteases, that is widely expressed in various cells and tissues.[59] CysC protein and its gene are upregulated in AD brains, posing a risk factor for late-onset AD.[60,61] CysC does not affect production of cellular amyloid beta peptide (Aβ); however, overexpression of CysC in neurons leads to inhibition of GSK3β turnover, augmentation of GSK3β levels in neurons that promotes GSK3β-tau phosphorylation at Ser396/404, MT instability, and neurodegeneration.[62,63]. This evidence concerns the gene CST3 and Alzheimer disease.