Whole brain optoacoustic tomography reveals strain-specific regional beta-amyloid densities in Alzheimer`s disease amyloidosis models

Ni, R.; Dean-Ben, X. L.; Kirschenbaum, D.; Rudin, M.; Chen, Z.; Crimi, A.; Voigt, F.; Nilsson, P. R.; Helmchen, F.; Nitsch, R. M.; Aguzzi, A.; Razansky, D.; Klohs, J.

doi:10.1101/2020.02.25.964064

bioRxiv · 10.1101/2020.02.25.964064

Whole brain optoacoustic tomography reveals strain-specific regional beta-amyloid densities in Alzheimer`s disease amyloidosis models

Ni, R.·Dean-Ben, X. L.·Kirschenbaum, D.·Rudin, M.·Chen, Z.·Crimi, A.·Voigt, F.·Nilsson, P. R.·Helmchen, F.·Nitsch, R. M.·Aguzzi, A.·Razansky, D.·Klohs, J.

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Abstract

Deposition of beta-amyloid (A{beta}) deposits is one major histopathological hallmark of Alzheimers disease (AD). Here, we introduce volumetric multi-spectral optoacoustic tomography (vMSOT), which covers 10x10x10 mm3 field-of-view, capable of 3D whole mouse brain imaging. We show for the first time the optoacoustic properties of oxazine-derivative AOI987 probe, which binds to A{beta}, and the application of vMSOT for the quantification of brain-wide A{beta} deposition. Administration of AOI987 to two common transgenic mouse strains of AD amyloidosis led to a retention of the probe in A{beta}-laden brain regions. Co-registered of vMSOT data to a brain atlas revealed strain-specific pattern of AOI987 uptake. A comparison with ex vivo light-sheet microscopy in cleared mouse brains showed a good correspondence in A{beta} distribution. Lastly, we demonstrate the specificity of the AOI987 probe by immunohistochemistry. vMSOT with AOI987 facilitates preclinical brain region-specific studies of A{beta} spread and accumulation, and the monitoring of putative treatments targeting A{beta}.

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Ni, R., Dean-Ben, X. L., Kirschenbaum, D., Rudin, M., Chen, Z., Crimi, A., Voigt, F., Nilsson, P. R., Helmchen, F., Nitsch, R. M., Aguzzi, A., Razansky, D., Klohs, J.. 2020-02-25. Whole brain optoacoustic tomography reveals strain-specific regional beta-amyloid densities in Alzheimer`s disease amyloidosis models. https://doi.org/10.1101/2020.02.25.964064

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