%0 Journal Article
%A Jährling, Nina
%A Becker, Klaus
%A Wegenast-Braun, Bettina M
%A Grathwohl, Stefan A
%A Jucker, Mathias
%A Dodt, Hans-Ulrich
%T Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.
%J PLOS ONE
%V 10
%N 5
%@ 1932-6203
%C San Francisco, California, US
%I PLOS
%M DZNE-2020-04267
%P e0125418
%D 2015
%X 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.
%K Alkenes: analysis
%K Alkenes: metabolism
%K Amyloid beta-Protein Precursor: genetics
%K Amyloidosis: pathology
%K Animals
%K Benzene Derivatives: analysis
%K Benzene Derivatives: metabolism
%K Brain: pathology
%K Disease Models, Animal
%K Fluorescent Dyes: analysis
%K Fluorescent Dyes: metabolism
%K Humans
%K Imaging, Three-Dimensional: methods
%K Mice, Inbred C57BL
%K Mice, Transgenic
%K Microscopy: methods
%K Plaque, Amyloid: pathology
%K Stilbenes
%K 1,4-bis(4'-hydroxystyryl)-2-methoxybenzene (NLM Chemicals)
%K Alkenes (NLM Chemicals)
%K Amyloid beta-Protein Precursor (NLM Chemicals)
%K Benzene Derivatives (NLM Chemicals)
%K Fluorescent Dyes (NLM Chemicals)
%K Stilbenes (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26017149
%2 pmc:PMC4446269
%R 10.1371/journal.pone.0125418
%U https://pub.dzne.de/record/137945