Experimental evidence for the age dependence of tau protein spread in the brain

Sci Adv. 2019 Jun 26;5(6):eaaw6404. doi: 10.1126/sciadv.aaw6404. eCollection 2019 Jun.


The incidence of Alzheimer's disease (AD), which is characterized by progressive cognitive decline that correlates with the spread of tau protein aggregation in the cortical mantle, is strongly age-related. It could be that age predisposes the brain for tau misfolding and supports the propagation of tau pathology. We tested this hypothesis using an experimental setup that allowed for exploration of age-related factors of tau spread and regional vulnerability. We virally expressed human tau locally in entorhinal cortex (EC) neurons of young or old mice and monitored the cell-to-cell tau protein spread by immunolabeling. Old animals showed more tau spreading in the hippocampus and adjacent cortical areas and accumulated more misfolded tau in EC neurons. No misfolding, at any age, was observed in the striatum, a brain region mostly unaffected by tangles. Age and brain region dependent tau spreading and misfolding likely contribute to the profound age-related risk for sporadic AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Brain / metabolism*
  • Cell Line
  • Disease Models, Animal
  • Disease Progression
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / metabolism
  • tau Proteins / metabolism*


  • tau Proteins