Leucine Carboxyl Methyltransferase 1 Overexpression Protects Against Cognitive and Electrophysiological Impairments in Tg2576 APP Transgenic Mice

Background: The serine/threonine protein phosphatase, PP2A, is thought to play a central role in the molecular pathogenesis of Alzheimer’s disease (AD), and activity substrate specificity PP2A regulated, part, through methylation demethylation its catalytic subunit. Previously, we found that transgenic overexpression methyltransferase, LCMT-1, or methylesterase, PME-1, altered sensitivity mice impairments caused by acute exposure synthetic oligomeric amyloid-? (A?). Objective: Here sought test possibility these molecules also controlled chronically elevated levels A? produced vivo. Methods: To do this, examined effects PME-1 on cognitive electrophysiological chronic mutant human APP Tg2576 mice. Results: We LCMT-1 prevented short-term spatial memory synaptic plasticity mice, without altering expression soluble levels. While magnitude was small potentially confounded emergence non-cognitive impairments, overexpressed showed trend toward earlier onset and/or increased severity impairments. Conclusion: These data suggest may participate AD regulating pathogenic A?.