title: Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.
abstract: Alzheimer´s disease (AD) is the most common neurodegenerative disorder. AD neuropathology is characterized by intracellular neurofibrillary tangles and extracellular β-amyloid deposits in the brain. To elucidate the complexity of AD pathogenesis a variety of transgenic mouse models have been generated. An ideal imaging system for monitoring β-amyloid plaque deposition in the brain of these animals should allow 3D-reconstructions of β-amyloid plaques via a single scan of an uncropped brain. Ultramicroscopy makes this possible by replacing mechanical slicing in standard histology by optical sectioning. It allows a time efficient analysis of the amyloid plaque distribution in the entire mouse brain with 3D cellular resolution. We herein labeled β-amyloid deposits in a transgenic mouse model of cerebral β-amyloidosis (APPPS1 transgenic mice) with two intraperitoneal injections of the amyloid-binding fluorescent dye methoxy-X04. Upon postmortem analysis the total number of β-amyloid plaques, the β-amyloid load (volume percent) and the amyloid plaque size distributions were measured in the frontal cortex of two age groups (2.5 versus 7-8.5 month old mice). Applying ultramicroscopy we found in a proof-of-principle study that the number of β-amyloid plaques increases with age. In our experiments we further observed an increase of large plaques in the older age group of mice. We demonstrate that ultramicroscopy is a fast, and accurate analysis technique for studying β-amyloid lesions in transgenic mice allowing the 3D staging of β-amyloid plaque development. This in turn is the basis to study neural network degeneration upon cerebral β-amyloidosis and to assess Aβ-targeting therapeutics.
authors.affiliation: Department of Bioelectronics, FKE, Vienna University of Technology, Vienna, Austria; Section of Bioelectronics, Center for Brain Research (MUW), Vienna, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Jährling
authors.affiliation: Department of Bioelectronics, FKE, Vienna University of Technology, Vienna, Austria; Section of Bioelectronics, Center for Brain Research (MUW), Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Wegenast-Braun
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Grathwohl
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
authors.affiliation: Department of Bioelectronics, FKE, Vienna University of Technology, Vienna, Austria; Section of Bioelectronics, Center for Brain Research (MUW), Vienna, Austria.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Dodt
mesh_terms: D000475:Alkenes / Q000032:analysis / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000473:pathology*; D000818:Animals; D001555:Benzene Derivatives / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000032:analysis / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008853:Microscopy / Q000379:methods*; D058225:Plaque, Amyloid / Q000473:pathology*; D013267:Stilbenes
chemical_list: C465418:1,4-bis(4'-hydroxystyryl)-2-methoxybenzene; D000475:Alkenes; D016564:Amyloid beta-Protein Precursor; D001555:Benzene Derivatives; D005456:Fluorescent Dyes; D013267:Stilbenes