Accelerated Tau Aggregation, Apoptosis and Neurological Dysfunction Caused by Chronic Oral Administration of Aluminum in a Mouse Model of Tauopathies

To clarify whether long‐term oral ingestion of aluminum ( A l) can increase tau aggregation in mammals, we examined the effects of oral A l administration on tau accumulation, apoptosis in the central nervous system ( CNS ) and motor function using tau transgenic ( T g) mice that show very slowly progressive tau accumulation. A l‐treated tau T g mice had almost twice as many tau‐positive inclusions in the spinal cord as tau T g mice without A l treatment at 12 months of age, a difference that reached statistical significance, and the development of pretangle‐like tau aggregates in the brain was also significantly advanced from 9 months. A l exposure did not induce any tau pathology in wild‐type ( WT ) mice. Apoptosis was observed in the hippocampus in A l‐treated tau T g mice, but was virtually absent in the other experimental groups. Motor function as assessed by the tail suspension test was most severely impaired in A l‐treated tau T g mice. Given our results, chronic oral ingestion of A l may more strongly promote tau aggregation, apoptosis and neurological dysfunction if individuals already had a pathological process causing tau aggregation. These findings may also implicate chronic A l neurotoxicity in humans, who frequently have had mild tau pathology from a young age.