Deposition of beta-amyloid deposits is one major histopathological hallmark of Alzheimer′s disease (AD). Here, we introduce volumetric multi-spectral optoacoustic tomography (vMSOT), which covers 10×10×10 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 beta-amyloid, and the application of vMSOT for the quantification of brain-wide beta-amyloid; deposition. Administration of

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... 7 to two common transgenic mouse strains of AD amyloidosis led to a retention of the probe in beta-amyloid-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 beta-amyloid; distribution. Lastly, we demonstrate the specificity of the AOI987 probe by immunohistochemistry. vMSOT with AOI987 facilitates preclinical brain region-specific studies of beta-amyloid; spread and accumulation, and the monitoring of putative treatments targeting beta-amyloid;.