Neurofibrillary tangles (NFTs) are associated with many neurodegenerative disorders, such as Alzheimer's disease (AD). The major components of NFTs are hyper-phosphorylated tau proteins. The alternatively spliced form of the presenilin-2 (PS2) gene (PS2V) has been observed in sporadic AD brains. However, it is not known whether there is a relationship between tau aggregation/hyper-phosphorylation and PS2V expression. In this manuscript, we make the first report of PS2V alterations in the conformation of the tau protein (unknown form of tau) in the human neuroblastoma cell line.