Adriano Aguzzi, Switzerland
Universitätsspital Zurich NeuropathologyAuthor Of 1 Presentation
HIGH PRECISION IN VIVO ASSESSMENT OF ALZHEIMER'S BETA-AMYLOID DEPOSITS WITH MULTI-SCALE IMAGING-FROM SINGLE PLAQUE TO WHOLE BRAIN MAPPING
Abstract
Aims
Non-invasive high-resolution imaging of amyloid-beta (Aβ) deposits across the entire rodent brain can greatly advance our understanding on the underlying pathophysiology of Alzheimer's disease. At present, a large gap exists between sub-millimeter scale highly invasive intravital microscopy and whole-brain imaging modalities lacking the resolution or molecular specificity for accurate characterization of Aβ pathologies. Here we introduce a multi-scale optical molecular imaging platform from transcranial observations of single plaques to 3D whoe brain Aβ mapping in animal models.
Methods
The in vitro binding between amyloid probes AOI987 and luminescent conjugated oligothiophene HS-169 and recombinant Aβ1-42 fibrils were assessed. High precision in vivo assessment of Aβ deposits was performed in transgenic APP/PS1, arcAβ mice and wild-type littermates (12-24 months-old) with newly devised large-field multifocal illumination fluorescence microscopy using luminacient conjugated oligothiophene HS-169 and multi-view volumetric multispectral optoacoustic tomography using oxazine-derivative AOI987 probe. Ex vivo light-sheet microscopy and immunohistochemistry was performed at ex vivo to assess the specificity of the probes binding to Aβ.
Results
We achieved transcranial cortex-wide Aβ imaging with 10 μm (single plaque) resolution, scaling into 100 μm resolution imaging at the whole brain level, including deeply embedded areas such as hippocampus and thalamus inaccessible by conventional intravital microscopy. Ex vivo light-sheet microscopy and immunohistochemistry confirmed the specificity and regional distributions unveiled by in vivo Aβ imaging.
Conclusions
We developed a novel in vivo Aβ imaging pipeline for multi-scale high precision assessment, which facilitates region-specific studies of Aβ spread and accumulation, and the monitoring of putative treatments targeting Alzheimer’s disease.