TY  - JOUR
AU  - Jährling, Nina
AU  - Becker, Klaus
AU  - Wegenast-Braun, Bettina M
AU  - Grathwohl, Stefan A
AU  - Jucker, Mathias
AU  - Dodt, Hans-Ulrich
TI  - Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.
JO  - PLOS ONE
VL  - 10
IS  - 5
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - DZNE-2020-04267
SP  - e0125418
PY  - 2015
AB  - 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.
KW  - Alkenes: analysis
KW  - Alkenes: metabolism
KW  - Amyloid beta-Protein Precursor: genetics
KW  - Amyloidosis: pathology
KW  - Animals
KW  - Benzene Derivatives: analysis
KW  - Benzene Derivatives: metabolism
KW  - Brain: pathology
KW  - Disease Models, Animal
KW  - Fluorescent Dyes: analysis
KW  - Fluorescent Dyes: metabolism
KW  - Humans
KW  - Imaging, Three-Dimensional: methods
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Microscopy: methods
KW  - Plaque, Amyloid: pathology
KW  - Stilbenes
KW  - 1,4-bis(4'-hydroxystyryl)-2-methoxybenzene (NLM Chemicals)
KW  - Alkenes (NLM Chemicals)
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Benzene Derivatives (NLM Chemicals)
KW  - Fluorescent Dyes (NLM Chemicals)
KW  - Stilbenes (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26017149
C2  - pmc:PMC4446269
DO  - DOI:10.1371/journal.pone.0125418
UR  - https://pub.dzne.de/record/137945
ER  -