A major challenge for diagnosing and monitoring the progression of amyloid-based diseases is the capability to distinguish between amyloid deposits that are associated with related, but distinctly different, diseases. Here, we demonstrate that Amino Naphthalenyl-2-Cyano-Acrylate (ANCA)-based probes can fluorescently discriminate between different types of amyloid deposits in brain. This discriminating behavior is due to the stabilization of the ground versus excited states of these probes as a function of the polarity of their microenvironment (i.e. within the binding pocket on the amyloid). This property makes it possible for the first time to estimate the inherent static relative permittivity of the binding pocket of each amyloid within tissue. The capability to selectively follow the deposition of specific amyloids in tissue may provide important information for therapeutic development that is not readily accessible from currently available technology.
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