Details

Autor(en) / Beteiligte

• Whitesell, Jennifer D.
• Buckley, Alex R.
• Knox, Joseph E.
• Kuan, Leonard
• Graddis, Nile
• Pelos, Andrew
• Mukora, Alice
• Wakeman, Wayne
• Bohn, Phillip
• Ho, Anh
• Hirokawa, Karla E.
• Harris, Julie A.

Titel

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

Ist Teil von

• Journal of comparative neurology (1911), 2019-09, Vol.527 (13), p.2122-2145

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 age in three APP‐overexpression mouse lines (APP/PS1, Tg2576, and 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 two‐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; for example, 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. We used high‐throughput serial two‐photon imaging and automated informatics processing to map the brain‐wide distribution of Aβ plaques in three APP‐overexpression mouse lines (APP/PS1, Tg2576, and hAPP‐J20). We show how whole brain imaging of amyloid pathology in mice reveals the extent that each model recapitulates Aβ deposition patterns described in Alzheimer's disease.