Spectral Discrimination of Cerebral Amyloid Lesions after Peripheral Application of Luminescent Conjugated Oligothiophenes

• In vivo imaging of pathological protein aggregates provides essential knowledge of the kinetics and implications of these lesions in the progression of proteopathies, such as Alzheimer disease. Luminescent conjugated oligothiophenes are amyloid-specific ligands that bind and spectrally distinguish different types of amyloid aggregates. Herein, we report that heptamer formyl thiophene acetic acid (hFTAA) passes the blood-brain barrier after systemic administration and specifically binds to extracellular beta-amyloid deposits in the brain parenchyma (A beta plaques) and in the vasculature (cerebral beta-amyloid angiopathy) of beta-amyloid precursor protein transgenic APP23 mice. Moreover, peripheral application of hFIAA also stained intracellular lesions of hyperphosphorylated Tau protein in P301S Tau transgenic mice. Spectral profiling of all three amyloid types was acquired ex vivo using two-photon excitation. hFTAA revealed a distinct shift in its emission spectra when bound to A beta plaques versus Tau lesions. Furthermore, a spectral shift was observed for A beta plaques versus cerebral beta-amyloid angiopathy, indicating that different amyloid types and structural variances of a specific amyloid type can be distinguished. In conclusion, by adding spectral signatures to amyloid lesions, our results pave the way for a new area of in vivo amyloid imaging, allowing in vivo differentiation of amyloid (sub)types and monitoring changes of their structure/composition over time. (Am J Pathol 2012, 181: 1953-1960 http://dx.doi.org/10.1016/j.ajpath.2012.08.031)

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