Advanced

High-Resolution 3D Reconstruction Reveals Intra-Synaptic Amyloid Fibrils

Capetillo-Zarate, Estibaliz; Gracia, Luis; Yu, Fangmin; Banfelder, Jason R.; Lin, Michael T.; Tampellini, Davide LU and Gouras, Gunnar LU (2011) In American Journal of Pathology 179(5). p.2551-2558
Abstract
beta-Amyloid (A beta) accumulation and aggregation are hallmarks of Alzheimer's disease (AD). High-resolution three-dimensional (HR-3D) volumetric imaging allows for better analysis of fluorescence confocal microscopy and 3D visualization of All pathology in brain. Early intraneuronal A beta pathology was studied in AD transgenic mouse brains by HR-3D volumetric imaging. To better visualize and analyze the development of A beta pathology, thioflavin S staining and immunofluorescence using antibodies against A beta, fibrillar A beta, and structural and synaptic neuronal proteins were performed in the brain tissue of Tg19959, wild-type, and Tg19959-YFP mice at different ages. Images obtained by confocal microscopy were reconstructed into... (More)
beta-Amyloid (A beta) accumulation and aggregation are hallmarks of Alzheimer's disease (AD). High-resolution three-dimensional (HR-3D) volumetric imaging allows for better analysis of fluorescence confocal microscopy and 3D visualization of All pathology in brain. Early intraneuronal A beta pathology was studied in AD transgenic mouse brains by HR-3D volumetric imaging. To better visualize and analyze the development of A beta pathology, thioflavin S staining and immunofluorescence using antibodies against A beta, fibrillar A beta, and structural and synaptic neuronal proteins were performed in the brain tissue of Tg19959, wild-type, and Tg19959-YFP mice at different ages. Images obtained by confocal microscopy were reconstructed into three-dimensional volumetric datasets. Such volumetric imaging of CA1 hippocampus of AD transgenic mice showed intraneuronal onset of A beta 42 accumulation and fibrillization within cell bodies, neurites, and synapses before plaque formation. Notably, early fibrillar A beta was evident within individual synaptic compartments, where it was associated with abnormal morphology. In dendrites, increasing intraneuronal thioflavin S correlated with decreases in neurofilament marker SMI32. Fibrillar A beta aggregates could be seen piercing the cell membrane. These data support that A beta fibrillization begins within AD vulnerable neurons, leading to disruption of cytoarchitecture and degeneration of spines and neurites. Thus, HR-3D volumetric image analysis allows for better visualization of intraneuronal A beta pathology and provides new insights into plaque formation in AD. (Am J Pathol 2011, 170:2551-2558. DOI: 10.1016/j.ajpath.2011.07.045) (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
179
issue
5
pages
2551 - 2558
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000298307600038
  • scopus:80054974015
ISSN
1525-2191
DOI
10.1016/j.ajpath.2011.07.045
language
English
LU publication?
yes
id
b55acffc-3dd7-4477-91b9-e648da9462d4 (old id 2313144)
date added to LUP
2012-02-01 07:35:32
date last changed
2017-09-17 03:47:45
@article{b55acffc-3dd7-4477-91b9-e648da9462d4,
  abstract     = {beta-Amyloid (A beta) accumulation and aggregation are hallmarks of Alzheimer's disease (AD). High-resolution three-dimensional (HR-3D) volumetric imaging allows for better analysis of fluorescence confocal microscopy and 3D visualization of All pathology in brain. Early intraneuronal A beta pathology was studied in AD transgenic mouse brains by HR-3D volumetric imaging. To better visualize and analyze the development of A beta pathology, thioflavin S staining and immunofluorescence using antibodies against A beta, fibrillar A beta, and structural and synaptic neuronal proteins were performed in the brain tissue of Tg19959, wild-type, and Tg19959-YFP mice at different ages. Images obtained by confocal microscopy were reconstructed into three-dimensional volumetric datasets. Such volumetric imaging of CA1 hippocampus of AD transgenic mice showed intraneuronal onset of A beta 42 accumulation and fibrillization within cell bodies, neurites, and synapses before plaque formation. Notably, early fibrillar A beta was evident within individual synaptic compartments, where it was associated with abnormal morphology. In dendrites, increasing intraneuronal thioflavin S correlated with decreases in neurofilament marker SMI32. Fibrillar A beta aggregates could be seen piercing the cell membrane. These data support that A beta fibrillization begins within AD vulnerable neurons, leading to disruption of cytoarchitecture and degeneration of spines and neurites. Thus, HR-3D volumetric image analysis allows for better visualization of intraneuronal A beta pathology and provides new insights into plaque formation in AD. (Am J Pathol 2011, 170:2551-2558. DOI: 10.1016/j.ajpath.2011.07.045)},
  author       = {Capetillo-Zarate, Estibaliz and Gracia, Luis and Yu, Fangmin and Banfelder, Jason R. and Lin, Michael T. and Tampellini, Davide and Gouras, Gunnar},
  issn         = {1525-2191},
  language     = {eng},
  number       = {5},
  pages        = {2551--2558},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {High-Resolution 3D Reconstruction Reveals Intra-Synaptic Amyloid Fibrils},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2011.07.045},
  volume       = {179},
  year         = {2011},
}