A, B. Fluorescence of 7-hydroxy-3H-phenoxazin-3-one (resorufin) to 1,4-bis(3-carboxy-4-hydroxyphenylethenyl)-benzene (X-34) or compound 2 applied directly to tissue sections from a 12-month old APP/PS1 mouse (A–D) and an AD case (E–H). Resorufin fluorescence is seen in CAA (A, pink arrow) but not plaques (green arrows in B); labeling of both CAA and plaques with X-34 overstaining of the same tissue section is shown in B. C, D. Two-photon microscopy images of resorufin after infusion into the brain through a cranial window of a 12-month old APP/PS1 mouse. Resorufin labeled both CAA (C, pink arrows) and plaques (C, green arrows). Subsequent infusion of compound 2 resulted in overstaining of the same CAA and plaques labeled with resorufin (D). E–H. In tissue sections of occipital cortex from an AD case, resorufin fluorescence is seen in both plaques (E, green arrows) and CAA (G, pink arrow). Overstaining of the same tissue section with X-34 resulted in comparable fluorescent signal in the same structures (F, H). X-34 also labeled neurofibrillary tangles (NFT, yellow arrows, F). Scale bar = 75 μm (A–F); 40 μm (G, H).