In this thesis study we examined glycogen synthase kinase-3β (GSK-3β) and its effects over Nrf2 and Pin 1 as it relates to Alzheimer’s disease (AD). AD is a neurodegenerative disease characterized by a prolonged high oxidative environment. Transcription factor Nrf2 is vital in the brain’s defense against oxidative insults through its up-regulation of over 100 antioxidants. Depletion of the brain’s antioxidant defense system results in intolerance to an oxidative environment, contributing to the progression of AD. The regulatory Pin 1 protein promotes cellular homeostasis, and when down-regulated results in increased deposits of neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques, the two pathological hallmarks of AD. Using aged SAMP8 mice treated with antisense oligonucleotide (AO) directed at GSK-3β and random AO, the data presented here demonstrate decreased oxidative stress and increased Nrf2 transcriptional activity and Pin 1 levels as a result of the down-regulation of GSK-3β. Collectively, these results implicate GSK-3β activity in the increased oxidative stress of AD and support its inhibition as a possible therapeutic treatment for the disease. Further, we elucidate a possible mechanism connecting GSK-3β to the loss of tolerance to an oxidative environment and increased deposits of NFTs and Aβ plaques observed in AD.