MAPT and Alzheimer disease: Prevents protein aggregation: In the context of AD development, estradiol increases PP2a, causing dephosphorylation of tau and stabilizing the cytoskeleton. Estradiol inhibits BACE1, the enzyme that cleaves APP to its pathological form, the antecedent to amyloid plaque formation (69). Estradiol promotes expression of neprilysin, an enzyme that degrades amyloid (74).