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PDAPP; YFP double transgenic mice: a tool to study amyloid-beta associated changes in axonal, dendritic, and synaptic structures.

Publication ,  Journal Article
Brendza, RP; O'Brien, C; Simmons, K; McKeel, DW; Bales, KR; Paul, SM; Olney, JW; Sanes, JR; Holtzman, DM
Published in: J Comp Neurol
February 17, 2003

Neuritic plaques are one of the stereotypical hallmarks of Alzheimer's disease (AD) pathology. These structures are composed of extracellular accumulations of fibrillar forms of the amyloid-beta peptide (Abeta), a variety of other plaque-associated proteins, activated glial cells, and degenerating nerve processes. To study the neuritic toxicity of different structural forms of Abeta in the context of regional connectivity and the entire cell, we crossed PDAPP transgenic (Tg) mice, a model with AD-like pathology, to Tg mice that stably express yellow fluorescent protein (YFP) in a subset of neurons in the brain. In PDAPP; YFP double Tg mice, markedly enlarged YFP-labeled axonal and dendritic varicosities were associated with fibrillar Abeta deposits. These varicosities were absent in areas where there were nonfibrillar Abeta deposits. Interestingly, YFP-labeled varicosities revealed changes that corresponded with changes seen with electron microscopy and the de Olmos silver staining technique. Other silver staining methods and immunohistochemical localization of phosphorylated neurofilaments or phosphorylated tau were unable to detect the majority of these dystrophic neurites. Some but not all synaptic vesicle markers accumulated abnormally in YFP-labeled varicosities associated with neuritic plaques. In addition to the characterization of the effects of Abeta on axonal and dendritic structure, YFP-labeled neurons in Tg mice should prove to be a valuable tool to interpret the localization patterns of other markers and for future studies examining the dynamics of axons and dendrites in a variety of disease conditions in living tissue both in vitro and in vivo.

Duke Scholars

Published In

J Comp Neurol

DOI

ISSN

0021-9967

Publication Date

February 17, 2003

Volume

456

Issue

4

Start / End Page

375 / 383

Location

United States

Related Subject Headings

  • Synaptic Vesicles
  • Silver Staining
  • Presynaptic Terminals
  • Neurons
  • Neurology & Neurosurgery
  • Neurites
  • Microscopy, Electron
  • Mice, Transgenic
  • Mice
  • Luminescent Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brendza, R. P., O’Brien, C., Simmons, K., McKeel, D. W., Bales, K. R., Paul, S. M., … Holtzman, D. M. (2003). PDAPP; YFP double transgenic mice: a tool to study amyloid-beta associated changes in axonal, dendritic, and synaptic structures. J Comp Neurol, 456(4), 375–383. https://doi.org/10.1002/cne.10536
Brendza, Robert P., Cara O’Brien, Kelly Simmons, Daniel W. McKeel, Kelly R. Bales, Steven M. Paul, John W. Olney, Joshua R. Sanes, and David M. Holtzman. “PDAPP; YFP double transgenic mice: a tool to study amyloid-beta associated changes in axonal, dendritic, and synaptic structures.J Comp Neurol 456, no. 4 (February 17, 2003): 375–83. https://doi.org/10.1002/cne.10536.
Brendza RP, O’Brien C, Simmons K, McKeel DW, Bales KR, Paul SM, et al. PDAPP; YFP double transgenic mice: a tool to study amyloid-beta associated changes in axonal, dendritic, and synaptic structures. J Comp Neurol. 2003 Feb 17;456(4):375–83.
Brendza, Robert P., et al. “PDAPP; YFP double transgenic mice: a tool to study amyloid-beta associated changes in axonal, dendritic, and synaptic structures.J Comp Neurol, vol. 456, no. 4, Feb. 2003, pp. 375–83. Pubmed, doi:10.1002/cne.10536.
Brendza RP, O’Brien C, Simmons K, McKeel DW, Bales KR, Paul SM, Olney JW, Sanes JR, Holtzman DM. PDAPP; YFP double transgenic mice: a tool to study amyloid-beta associated changes in axonal, dendritic, and synaptic structures. J Comp Neurol. 2003 Feb 17;456(4):375–383.
Journal cover image

Published In

J Comp Neurol

DOI

ISSN

0021-9967

Publication Date

February 17, 2003

Volume

456

Issue

4

Start / End Page

375 / 383

Location

United States

Related Subject Headings

  • Synaptic Vesicles
  • Silver Staining
  • Presynaptic Terminals
  • Neurons
  • Neurology & Neurosurgery
  • Neurites
  • Microscopy, Electron
  • Mice, Transgenic
  • Mice
  • Luminescent Proteins