Impairment of epigenetic gene control mechanisms in the brain involving histone acetylation causes significant cognitive deficits that are a debilitating hallmark of most neurodegenerative disorders, including Alzheimer’s disease (AD). My laboratory is focused on understanding the mechanisms that govern epigenetic regulation of higher order brain function. Recently, we made the exciting discovery that epigenetic Tip60 histone acetylation (HAT) action is critical for cognitive processes and remarkably, plays a neuroprotective role under in vivo disease state neurodegenerative conditions. We are currently exploring the mechanisms underlying neural Tip60 HAT function in neuroprotective epigenetic gene control and the beneficial impact that environmental enrichment conditions has on these processes. Our studies should provide new understanding into epigenetic-based mechanisms underlying neurodegenerative disorders, and broad insights into HAT based drug design for early therapeutic intervention of cognitive deficits.