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:
https://lup.lub.lu.se/record/2313144
- author
- Capetillo-Zarate, Estibaliz
; Gracia, Luis
; Yu, Fangmin
; Banfelder, Jason R.
; Lin, Michael T.
; Tampellini, Davide
LU
and Gouras, Gunnar
LU
- organization
- publishing date
- 2011
- 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
- pmid:21925470
- 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
- 2016-04-01 10:32:33
- date last changed
- 2022-05-05 23:08:11
@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}},
doi = {{10.1016/j.ajpath.2011.07.045}},
volume = {{179}},
year = {{2011}},
}