Passive immunotherapy rapidly increases structural plasticity in a mouse model of Alzheimer disease

Tara L Spires-Jones, Matthew L Mielke, Anete Rozkalne, Melanie Meyer-Luehmann, Alix de Calignon, Brian J Bacskai, Dale Schenk, Bradley T Hyman

Research output: Contribution to journalArticlepeer-review


Senile plaque-associated changes in neuronal connectivity such as altered neurite trajectory, dystrophic swellings, and synapse and dendritic spine loss are thought to contribute to cognitive dysfunction in Alzheimer's disease and mouse models. Immunotherapy to remove amyloid beta is a promising therapy that causes recovery of neurite trajectory and dystrophic neurites over a period of days. The acute effects of immunotherapy on neurite morphology at a time point when soluble amyloid has been cleared but dense plaques are not yet affected are unknown. To examine whether removal of soluble amyloid beta (Abeta) has a therapeutic effect on dendritic spines, we explored spine dynamics within 1 h of applying a neutralizing anti Abeta antibody. This acute treatment caused a small but significant increase in dendritic spine formation in PDAPP brain far from plaques, without affecting spine plasticity near plaques or average dendritic spine density. These data support the hypothesis that removing toxic soluble forms of amyloid-beta rapidly increases structural plasticity possibly allowing functional recovery of neural circuits.
Original languageEnglish
Pages (from-to)213-20
Number of pages8
JournalNeurobiology of disease
Issue number2
Publication statusPublished - Feb 2009


  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Analysis of Variance
  • Animals
  • Axons
  • Brain
  • Dendritic Spines
  • Disease Models, Animal
  • Humans
  • Immunization, Passive
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • Neurons
  • Plaque, Amyloid


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