Given the evidence implicating protein phosphatase 2A (PP2A) in the molecular pathogenesis of tauopathies, we sought to determine whether manipulating the expression of enzymes that regulate PP2A activity, such as leucine carboxyl methyltransferase 1 (LCMT‐1) and protein methylesterase 1 (PME‐1), would alter pathological responses to oligomeric tau. This evidence concerns the gene PPME1 and tauopathy.