Transcranial in vivo detection of Aβ at single plaque resolution with large-field multifocal illumination fluorescence microscopy

The abnormal deposition of amyloid-beta proteins in the brain is one of the major histopathological hallmarks of Alzheimers′ disease. Currently available intravital microscopy techniques for high-resolution plaque visualization commonly involve highly invasive procedures and are limited to a small field-of-view within the rodent brain. Here, we report the transcranial detection of amyloid-beta deposits at the whole brain scale with 20 μm resolution in APP/PS1 and arcAβ mouse models of Alzheimer′s disease amyloidosis using a large-field multifocal illumination (LMI) fluorescence microscopy technique. Highly sensitive and specific detection of amyloid-beta deposits at a single plaque level in APP/PS1 and arcAβ mice was facilitated using luminescent conjugated oligothiophene HS-169. Immunohistochemical staining with HS-169, anti-Aβ antibody 6E10, and conformation antibodies OC (fibrillar) of brain tissue sections further showed that HS-169 resolved compact parenchymal and vessel-associated amyloid deposits. The novel imaging platform offers new prospects for in vivo studies into Alzheimer′s disease mechanisms in animal models as well as longitudinal monitoring of therapeutic responses at a single plaque level.