Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer's disease

FEBS Lett. 1999 Nov 19;461(3):329-33. doi: 10.1016/s0014-5793(99)01480-5.


Hyperphosphorylated tau is the major component of paired helical filaments in neurofibrillary tangles found in Alzheimer's disease brains, and tau hyperphosphorylation is thought to be a critical event in the pathogenesis of this disease. The objective of this study was to reproduce tau hyperphosphorylation in an animal model by inducing hypoglycemia. Food deprivation of mice for 1 to 3 days progressively enhanced tau hyperphosphorylation in the hippocampus, to a lesser extent in the cerebral cortex, but the effect was least in the cerebellum, in correspondence with the regional selectivity of tauopathy in Alzheimer's disease. This hyperphosphorylation was reversible by refeeding for 1 day. We discuss possible mechanisms of this phenomenon, and propose the starved mouse as a simple model to study in vivo tau phosphorylation and dephosphorylation which are altered in Alzheimer's disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / metabolism*
  • Cerebellum / metabolism
  • Cerebral Cortex / metabolism
  • Disease Models, Animal*
  • Food Deprivation
  • Glucose / metabolism
  • Hippocampus / metabolism
  • Hypoglycemia / etiology
  • Hypoglycemia / metabolism*
  • Insulin / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational*
  • Starvation / complications
  • Starvation / metabolism*
  • tau Proteins / metabolism*


  • Insulin
  • tau Proteins
  • Protein Kinases
  • Glucose