Contributors: Radiopharmaceutical and Neurochemical Biomarkers (CRNL-BIORAN); Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Synchrotron SOLEIL (SSOLEIL); Centre National de la Recherche Scientifique (CNRS); ALBA Synchrotron light source Barcelone; Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL); Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Hospices Civils de Lyon (HCL); Unité Maladies Neuro-Dégénératives (MND); Laboratoire de Lyon ANSES; Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES); Institute for Biomedical Engineering ETH Zürich (IBT); Universität Zürich Zürich = University of Zurich (UZH)-Department of Information Technology and Electrical Engineering Zürich (D-ITET); Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology Zürich (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology Zürich (ETH Zürich); Faculty of Biology, Medicine and Health Manchester, UK; University of Manchester Manchester; Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA); Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN); Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Institut des sciences biologiques - CNRS Biologie (INSB-CNRS); ANR-11-EQPX-0031,NANOIMAGESX,Construction et exploitation d'une ligne de nanotomographie au synchrotron SOLEIL(2011); ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011); ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011)
Abstract: Accepted manuscript (author version after peer review) ; International audience ; Amyloid-β (Aβ) plaques from Alzheimer’s Disease (AD) can be visualized ex vivo in label-free brain samples using synchrotron X-ray phase-contrast tomography (XPCT). However, for XPCT to be useful as a screening method for amyloid pathology, it is essential to understand which factors drive the detection of Aβ plaques. The current study was designed to test the hypothesis that Aβ-related contrast in XPCT could be caused by the Aβ fibrils and/or by metals trapped in the plaques. Fibrillar and elemental compositions of Aβ plaques were probed in brain samples from different types of AD patients and AD models to establish a relationship between XPCT contrast and Aβ plaque characteristics. XPCT, micro-Fourier-Transform Infrared spectroscopy and micro-X-Ray Fluorescence spectroscopy were conducted on human samples (one genetic and one sporadic case) and on four transgenic rodent strains (mouse: APPPS1, ArcAβ, J20; rat: TgF344). Aβ plaques from the genetic AD patient were visible using XPCT, and had higher β–sheet content and higher metal levels than the sporadic AD patient, which remained undetected by XPCT. Aβ plaques in J20 mice and TgF344 rats appeared hyperdense on XPCT images, while they were hypodense with an hyperdense core in the case of APPPS1 and ArcAβ mice. In all four transgenic strains, β-sheet content was similar, while metal levels were highly variable: J20 (zinc and iron) and TgF344 (copper) strains showed greater metal accumulation than APPPS1 and ArcAβ mice. Hence, a hyperdense contrast formation of Aβ plaques in XPCT images was associated with biometal entrapment within plaques.
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