The deposition of beta-amyloid and tau are hallmarks of Alzheimer`s disease.It has been implicated in neuronal dysfunction, ultimately leading to cognitive impairment and dementia. Techniques to visualize these processes in animal models of the disease are highly desirable. However, microscopic imaging approaches have a limited coverage and are invasive. Non-invasive techniques on the other hand have either low sensitivity or low spatial resolution. In a clever approach, Jan Klohs and Ruiqing Ni from the Institute for Regenerative Medicine and the Institute of Biomedical Engineering, aimed at overcoming these shortcomings.
Our approach is based on optoacoustic imaging of molecular probes that can bind to tau and beta-amyloid. Light in the near-infrared range is used to excite these probes and detect the emitted vibrational waves, that result from the absorption of the light. This approach allows to deeply penetrate tissue with light and to achieve a high spatial resolution of ultrasound.
Klohs and Ni screened and tested several different optoacoustic probes, that can bind to tau and beta-amyloid. They showed that the deposition can be visualized and quantified non-invasively in mouse models, covering the entire brain with high spatial resolution. The non-invasive nature and spatial resolution of the tools allow to study the accumulation and spread of beta-amyloid and tau in the mouse brain over the entire disease course. Moreover, mechanistic studies and pharmacological interventions targeted against beta-amyloid and tau can be performed, where effects can be directly monitored. This will help us to understand the role of these proteins in the pathogenesis of Alzheimer`s and to evaluate novel therapies.
By: Ruiqing Ni and Jan Klohs, Institute for Biomedical Engineering, ETH & UZH; Institute for Regenerative Medicine, UZH.
References: Ni, R., Villois, A., Dean-Ben, X.L., Chen, Z., Vaas, M., Stavrakis, S., Shi, G., deMello, A., Ran, C., Razansky, D., Arosio, P., Klohs, J. In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice. Photoacoustics (2021).
Ni, R., Chen, Z., Gerez, J.A., Shi, G., Zhou, Q., Riek, R., Nilsson, K.P.R., Razansky, D., Klohs, J. Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy. Biomed Opt Express (2020).
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This work has been accomplished in collaboration with the lab of Prof. Razansky who has recently developed new scalable optoacoustic methods for noninvasive functional and molecular imaging across the entire rodent brain