Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer's disease-like tau pathology.

TitleInsulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer's disease-like tau pathology.
Publication TypeJournal Article
Year of Publication2017
AuteursGratuze, M, Julien, J, Petry, FR, Morin, F, Planel, E
JournalSci Rep
Volume7
Pagination46359
Date Published2017 Apr 12
ISSN2045-2322
Abstract

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer's disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ resulted in marked diabetes, and five low doses led to a milder diabetes. Both groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A), the main tau phosphatase. Interestingly, insulin injection 30 minutes before sacrifice partially restored tau phosphorylation to control levels in both STZ-injected groups. Our results confirm a link between insulin homeostasis and tau phosphorylation, which could explain, at least in part, a higher incidence of AD in diabetic patients.

DOI10.1038/srep46359
Alternate JournalSci Rep
PubMed ID28402338
PubMed Central IDPMC5389355