Methoxy-X04 is a brain-permeable fluorescent probe for amyloid-β (Aβ) to detect and quantify plaques, tangles, and cerebrovascular amyloid. It displays high in vitro binding affinity (Ki = 26.8 nM) for fibrillar β-sheet deposits and is used to image Aβ plaques in the brains of living APP/PS1 mice, a transgenic model of familial Alzheimer''s disease. For in vivo imaging, APP/PS1 mice were injected with methoxy-X04 at a dose of 10 mg/kg, i.p., 24 hours prior to two-photon imaging. Methoxy-X04 displays an excitation peak at 750 nm with emission between 460 and 500 nm.