In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories

J. D. D'Amore, S. T. Kajdasz, M. E. McLellan, B. J. Bacskai, E. A. Stern, Bradley T. Hyman

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Postmortem analyses of senile plaques reveal numerous dystrophic processes in their vicinity. We used in vivo multiphoton microscopy of a transgenic model of Alzheimer disease (AD) to simultaneously image senile plaques and nearby neuronal processes. Plaques were labeled by immunofluorescent staining or thioflavine-S and neuronal processes were labeled with a fluorescent dextran conjugate. Imaging of 3-dimensional volumes in the vicinity of plaques revealed subtle changes in neurite geometry in or near diffuse plaques. By contrast, disruptions in neurite morphology, including dystrophic neurites immediately surrounding plaques as well as major alterations in neurite trajectories, were seen in association with thioflavine-S-positive plaques. Nearly half of all labeled processes that came within 50 μm of a thioflavine-S-positive plaque were altered, suggesting a fairly large "halo" of neuropil alterations that extend beyond the discrete border of a thioflavine-S plaque. These results support the hypothesis that compact thioflavine-S-positive plaques disrupt the neuropil in AD.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number2
DOIs
StatePublished - 1 Feb 2003
Externally publishedYes

Keywords

  • Alzheimer disease
  • Amyloid-β
  • In vivo imaging
  • Multiphoton microscopy
  • Senile plaque
  • Transgenic mice

Fingerprint

Dive into the research topics of 'In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories'. Together they form a unique fingerprint.

Cite this