PIN1 and Alzheimer disease: Furthermore, lower levels of PIN1 may also increase the activity of GSK3β, which is associated with the phosphorylation of both amyloid precursor protein (APP) and multiple tau disease-associated phosphorylation sites.27, 28 Additionally, in the AD brain levels of p25 increase, which may in turn elevate CDK5 activity, which can promote the phosphorylation of the 231Thr-Pro site in tau, a known disease-associated event.29