Visualization of Apolipoprotein E-Binding Amyloid Plaques in Postmortem Alzheimer’s Disease Brains Using a Novel Fluorescent Probe THK-5320

(<i>E</i>)-2-(4-(dimethylamino)styryl)-<i>N</i>,<i>N</i>-dimethylquinolin-6-amine) (THK-5320) is a unique fluorescent compound that recognizes apolipoprotein E (ApoE)-binding amyloid plaques in postmortem human brain sections. To understand the distinctive characteristics of THK-5320 chemically and biologically, its fluorescence properties were investigated, and the association of the fluorescence wavelength with plaque subtypes and amyloid isoforms was explored. Blue plaques visualized with THK-5320 were consistent with those with anti-amyloid-β_1-16/amyloid-β_N3pE-stained antibodies, whereas red plaques visualized with THK-5320 were consistent with those with an ApoE-stained antibody in postmortem brain sections from patients with Alzheimer's disease. In contrast, the amyloid positron emission tomography (PET) tracer PiB and its fluorescent derivative did not show significant signals in ApoE-binding plaques, whereas the signals correlated well with those of amyloid-β_N3pE-positive plaques. Thus, THK-5320 may detect ApoE-binding amyloid plaques that conventional amyloid PET probes cannot detect. Multispectral fluorescence imaging with THK-5320 could be a useful tool to better understand the role of ApoE in amyloid pathology.