The present study suggests that microenvironmental stress, such as hypoxia or low glucose conditions, upregulates and widely expresses tau protein, which then travels to mitochondria via mitochondrial calcium transport and calcium uptake pathways. The tau protein contains mitochondrial-related domains HIG1, Calcium uniporter protein C-terminal, and Mff-like throughout the entire sequence.. This suggests that the tau protein will specifically target mitochondria when exposed to hypoxia or low glucose levels. Tau aggregation in the cytoplasm will ensue, potentially leading to neuroinflammation due to oxidative stress damage from mitochondrial damage.