Neural atrophy produced by AAV tau injections into hippocampus and anterior cortex of middle-aged mice.

Animal models of tauopathy help in understanding the role of mutations in tau pathobiology. Here, we used adeno-associated viral (AAV) vectors to administer three tau genetic variants (tau, tau, and tau) intracranially into 12-month-old C57BL/6Nia mice and collected tissue at 16 months. Vectors designed to express green fluorescent protein controlled for surgical procedures and exogenous protein expression by AAV. The tau genetic variants produced considerably different phenotypes. Tau and tau caused memory impairments. The tau caused increased amounts of aggregated tau, measured both neurochemically and histologically. Tau produced elevated levels of soluble tau and phosphorylated tau by ELISA and increased staining for phosphorylated forms of tau histologically. However, only the tau caused localized atrophy of brain tissue at the sites near the injection. The tau had low protein expression and produced no atrophy or memory impairments. This supports the potential use of AAV expressing tau in aged mice to examine events leading to neurodegeneration in Alzheimer's disease pathology.