Conversely, several authors described that in human SH-SY5Y neuroblastoma cells [59, 296] and rat primary cortical neurons [297], insulin exposure increased hyperphosphorylated tau protein levels, which was not transported into axons, thus accumulating and aggregating into NFTs in neuronal perikarya, and thereby promoting oxidative stress, apoptotic or necrotic death, and mitochondrial dysfunction associated with AD [30]. Here, INS is linked to Alzheimer disease.