Living Histopathology
Jesse Skoch (UCD), Brian Bacskai (Harvard), Bradley Hyman (Harvard)

Multiphoton microscopy
Alzheimer’s disease pathology (amyloid plaques and vascular amyloid angiopathy) in an aged living transgenic (PS-1 mutant) mouse. 2-photon microscopy with fluorescent thioflavin-T dye facilitates progressive observation of pathology development and efficacy of experimental therapeutics such as antibody therapy over days to months in living animals. This z-projection micrograph represents a series of scans aggregated over 200µm of cortical depth. Thioflavin-T dye binds with conformational specificity to the beta-pleated sheet structure found in the amyloid-beta peptide deposits of Alzheimer’s disease and undergoes a shift in both quantum yield (intensity) and spectrum (becomes green) upon binding. These excimer dye properties allow for enhanced specificity despite the difficulty of elevated background staining in live brain tissue.