Use of YFP to study amyloid-β associated neurite alterations in live brain slices

Robert P. Brendza, Kelly Simmons, Kelly R. Bales, Steven M. Paul, Mark P. Goldberg, David M. Holtzman

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Neuritic plaques are one of the defining neuropathological features of Alzheimer's disease (AD). These structures are composed of a buildup of fibrils of the amyloid-β (Aβ) peptide (amyloid) surrounded by activated glial cells and degenerating nerve processes (dystrophic neurites). To study neuritic plaques and possible abnormalities associated with dendrites, axons, and synaptic structures, we have developed an acute slice preparation model using PDAPP, yellow fluorescent protein (YFP) double transgenic mice (a mouse model with AD-like pathology that stably expresses YFP in a subset of neurons in the brain). With laser scanning confocal microscopy, we have imaged living brain slices from PDAPP, YFP double transgenic mice as old as 20 months and have been able to visualize axons, dendrites, dendritic spines, and dystrophic neurites for many hours. Our initial studies suggest that dystrophic axons and dendrites within neuritic plaques are fairly stable structures in the absence of exogenous perturbations. This acute slice preparation model should prove to be a useful tool to explore the pathophysiology of Aβ-related axonal, dendritic, and synaptic dysfunction.

Original languageEnglish
Pages (from-to)1071-1077
Number of pages7
JournalNeurobiology of Aging
Volume24
Issue number8
DOIs
StatePublished - Dec 2003

Keywords

  • Acute slice preparation
  • Alzheimer's disease
  • Amyloid
  • Confocal microscopy
  • Fluorescent protein
  • Neurite
  • Neuritic dystrophy
  • Transgenic mice

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