Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice

A fluorophore with peak excitation and emission wavelengths in the near-infrared window allows for the microscopic imaging of amyloid-beta and tau aggregates through the intact skull in mouse models of Alzheimer's disease. Non-invasive methods for the in vivo detection of hallmarks of Alzheimer's disease can facilitate the study of the progression of the disease in mouse models and may enable its earlier diagnosis in humans. Here we show that the zwitterionic heptamethine fluorophore ZW800-1C, which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to amyloid-beta deposits and to neurofibrillary tangles, and allows for the microscopic imaging of amyloid-beta and tau aggregates through the intact skull of mice. In transgenic mouse models of Alzheimer's disease, we compare the performance of ZW800-1C with that of the two spectrally similar heptamethine fluorophores ZW800-1A and indocyanine green, and show that ZW800-1C undergoes a longer fluorescence-lifetime shift when bound to amyloid-beta and tau aggregates than when circulating in blood vessels. ZW800-1C may prove advantageous for tracking the proteinic aggregates in rodent models of amyloid-beta and tau pathologies.

Automated summary

A fluorophore with peak near-infrared excitation and emission wavelengths enables imaging of amyloid-beta and tau aggregates in mouse models of Alzheimer's disease through intact skull. This non-invasive method facilitates the study of disease progression and potentially aids in early diagnosis in humans.