Age-dependent alterations in the presynaptic active zone in a Drosophila model of Alzheimer's disease

Neurobiol Dis. 2013 Mar;51:161-7. doi: 10.1016/j.nbd.2012.11.006. Epub 2012 Nov 10.


The accumulation of beta amyloid (Aβ) can cause synaptic impairments, but the characteristics and mechanisms of the synaptic impairment induced by the accumulation of Aβ in Alzheimer's disease (AD) remain unclear. In identified single neurons in a newly developed Drosophila AD model, in which Aβ accumulates intraneuronally, we found an age-dependent reduction in the synaptic vesicle release probability that was associated with a decrease in the density of presynaptic calcium channel clusters and an increase in the presynaptic and postsynaptic contact length. Moreover, these alterations occurred in the absence of presynaptic bouton loss. In addition, we found that Aβ expression also produced an age-dependent decrease in the amount of Bruchpilot (Brp), which plays an important role in controlling Ca(2+) channel clustering and synaptic vesicle release in the presynaptic active zone. Our study indicates that the chronic accumulation of intraneuronal Aβ can induce functional and structural changes in the presynaptic active zone prior to a loss of presynaptic buttons in the same neuron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Aging / physiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / adverse effects*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Drosophila melanogaster
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Patch-Clamp Techniques
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Synapses / ultrastructure*
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / ultrastructure


  • Amyloid beta-Peptides