Methoxy-X04, a derivative of Congo red and Chrysamine-G, is a brain-permeable fluorescent probe for amyloid-β (Aβ) [1].

Aβ peptides, proposed as a cause of Alzheimer’s disease, exists in multiple conformations, including soluble monomers, aggregated soluble oligomers, and insoluble fibrils. Soluble low-n molecular weight oligomers (including dimers and trimers, up to dodecamers) may be a major driver of neurotoxicity. Furthermore, soluble Aβ oligomers concentrate around the dense core of plaques, generating a neurotoxic halo that contributes to local neuritic dystrophy, synaptic loss, and neurodegeneration [2].

In in vitro binding studies, compared with Chrysamine-G (Ki = 25.3 nM), Methoxy-X04 exhibited similar binding affinity for Aβ fibrils (Ki = 26.8 nM) [1]. On brain slices of 12-month-old APP-PS1 (dE9) mice, 145 μM Methoxy-X04 was used for labelling fibrillary amyloid deposits [3].

In PS1/APP mice, a single i.v. injection of 5 to 10 mg/kg Methoxy-X04 distinguished individual plaques from brain fluorescent images, within 30 to 60 min after treatment. A single i.p. injection of 10 mg/kg Methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PS1/APP mouse brains [1].

References:

[1]. Klunk W E, Backsai B J, Mathis C A, et al. Imaging Aβ plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative. Journal of Neuropathology & Experimental Neurology, 2002, 61(9): 797-805.

[2]. Meilandt W J, Maloney J A, Imperio J, et al. Characterization of the selective in vitro and in vivo binding properties of crenezumab to oligomeric Aβ. Alzheimer's Research & Therapy, 2019, 11(1): 97.

[3]. Jung C K, Keppler K, Steinbach S, et al. Fibrillar amyloid plaque formation precedes microglial activation. PLoS One, 2015, 10(3): e0119768.