title: Spectral discrimination of cerebral amyloid lesions after peripheral application of luminescent conjugated oligothiophenes.
abstract: 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 β-amyloid deposits in the brain parenchyma (Aβ plaques) and in the vasculature (cerebral β-amyloid angiopathy) of β-amyloid precursor protein transgenic APP23 mice. Moreover, peripheral application of hFTAA 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 Aβ plaques versus Tau lesions. Furthermore, a spectral shift was observed for Aβ plaques versus cerebral β-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.
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Otfried-Mueller Strasse 2, Tübingen, Germany. bettina.braun@uni-tuebingen.de
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Wegenast-Braun
authors.forename: Angelos
authors.initials: A
authors.lastname: Skodras
authors.forename: Gonca
authors.initials: G
authors.lastname: Bayraktar
authors.forename: Jasmin
authors.initials: J
authors.lastname: Mahler
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Fritschi
authors.forename: Therése
authors.initials: T
authors.lastname: Klingstedt
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Mason
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Christian
authors.initials: C
authors.lastname: Liebig
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D049449:Luminescence; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D013194:Staining and Labeling; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000682:Amyloid; D013876:Thiophenes