Lentivirus Tau (P301S) expression in adult amyloid precursor protein (APP)-transgenic mice leads to tangle formation

Abstract

Aims: In this study, we aimed to investigate the interaction between amyloid- and Tau-associated pathologies to gain further insights into the development of Alzheimer's disease. We examined the formation of neurofibrillary tangles (NFT) in adult mouse brain without the prior overexpression of Tau at embryonic or early post-natal stages to dissociate any developmental mechanisms. Methods: Lentivirus technology was used to examine the effects of overexpressing mutant Tau-P301S in the adult mouse brains of both wild-type and amyloid precursor protein (APP)-transgenic mice. Results: We find that injection of lentivirus Tau-P301S into the hippocampus of adult wild-type mice increases levels of hyperphosphorylated Tau, as early as 3 months post injection. However, no NFT are found even after 13 months of Tau expression. In contrast, the overexpression of Tau-P301S in adult APP-transgenic animals results in the formation of Gallyas-stained NFT. Conclusions: Our current findings are the first to show that overexpression of Tau-P301S in adult mice overexpressing APP, but not wild-type mice, leads to enhanced Tau-related pathology. © 2008 Blackwell Publishing Ltd.