Abstract Over the past decades, classical drug development approaches for Alzheimer’s disease have yielded limited success, and this futileness has prompted scientists to seek non-classical approaches. In this report, we demonstrated that, with irradiation of LED light or with molecularly generated light (dubbed as “molecular light”) from chemiluminescence probe ADLumin-4, photolabile curcumin analogue CRANAD-147 could change properties, structures (sequences) and neurotoxicity of amyloid beta (Aβ) species in vitro. We further demonstrated that, with the assistance from molecular chemiluminescence imaging, the combination of CRANAD-147/LED or CRANAD-147/ADLumin-4 (molecular light) could slow down the accumulation of Aβs in transgenic 5xFAD mice in vivo. Due to the unlimited capacity of tissue penetration of molecular light in vivo, phototherapy with the combination of photolabile Aβ ligand and molecular light has great potential as an alternative approach for AD drug discovery.

Phototherapy with physically and molecularly produced light for Alzheimer’s disease