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

The abnormal deposition of beta-amyloid proteins in the brain is one of the major histopathological hallmarks of Alzheimer’s disease. Currently available intravital microscopy techniques can visualize plaques with high resolution, but are limited to a small field-of-view and with depth limitation. Here, we report the transcranial detection of amyloid-beta deposits at the whole brain scale with 20 mm resolution in APP/PS1 and arcAb mouse models of Alzheimer’s disease amyloidosis using a novel large-field multifocal illumination (LMI) fluorescence microscopy technique. High sensitive and specific detection of amyloid-beta deposits at single plaque level in APP/PS1 and arcAb mice was facilitated using luminescent conjugated oligothiophene HS-169. Immunohistochemical staining with HS-169, anti-Ab antibody 6E10, conformation antibodies OC (fibrillar) on brain tissue sections further showed that HS-169 resolved compact parenchymal and vessel-associated amyloid deposits. In conclusion, we demonstrate a new <em>in vivo </em>imaging platform for detection of amyloid-beta deposits at single plaque resolution in murine models of Alzheimer’s disease amyloidosis.