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Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer’s disease
- Publication Year :
- 2018
- Publisher :
- Cold Spring Harbor Laboratory, 2018.
-
Abstract
- A variety of Alzheimer’s disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across ages in three APP-overexpression mouse lines (APP/PS1, Tg2576, hAPP-J20) using in vivo labeling with methoxy-X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial 2-photon tomography and labeled plaques were detected using custom-built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain-wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP-J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; e.g., the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP-J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD.
- Subjects :
- 0303 health sciences
Amyloid pathology
biology
Amyloid beta
Hippocampal formation
03 medical and health sciences
0302 clinical medicine
Neuroimaging
Retrosplenial cortex
In vivo
mental disorders
biology.protein
Amyloid precursor protein
Cortical subplate
Neuroscience
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f5fac16b8d8c5eb1469e5495f2b8a6c3
- Full Text :
- https://doi.org/10.1101/395236