Widespread changes in dendritic spines in a model of Alzheimer's disease

Cereb Cortex. 2009 Mar;19(3):586-92. doi: 10.1093/cercor/bhn111. Epub 2008 Jul 16.


The mechanism by which dementia occurs in patients with Alzheimer's disease (AD) is not known. We assessed changes in hippocampal dendritic spines of APP/PS1 transgenic mice that accumulate amyloid beta throughout the brain. Three-dimensional analysis of 21,507 dendritic spines in the dentate gyrus, a region crucial for learning and memory, revealed a substantial decrease in the frequency of large spines in plaque-free regions of APP/PS1 mice. Plaque-related dendrites also show striking alterations in spine density and morphology. However, plaques occupy only 3.9% of the molecular layer volume. Because large spines are considered to be the physical traces of long-term memory, widespread decrease in the frequency of large spines likely contributes to the cognitive impairments observed in this AD model.

Publication types

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

MeSH terms

  • Alzheimer Disease / pathology*
  • Animals
  • Dendritic Spines / pathology*
  • Disease Models, Animal*
  • Mice
  • Mice, Transgenic