Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.
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 generat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4446269?pdf=render |
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| author | Nina Jährling Klaus Becker Bettina M Wegenast-Braun Stefan A Grathwohl Mathias Jucker Hans-Ulrich Dodt |
| author_facet | Nina Jährling Klaus Becker Bettina M Wegenast-Braun Stefan A Grathwohl Mathias Jucker Hans-Ulrich Dodt |
| author_sort | Nina Jährling |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T02:27:37Z |
| format | Article |
| id | doaj.art-62e0951ab2ef4e1e9d6e4ed07d0e702f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T02:27:37Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-62e0951ab2ef4e1e9d6e4ed07d0e702f2022-12-22T03:06:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012541810.1371/journal.pone.0125418Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.Nina JährlingKlaus BeckerBettina M Wegenast-BraunStefan A GrathwohlMathias JuckerHans-Ulrich DodtAlzheimer´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.http://europepmc.org/articles/PMC4446269?pdf=render |
| spellingShingle | Nina Jährling Klaus Becker Bettina M Wegenast-Braun Stefan A Grathwohl Mathias Jucker Hans-Ulrich Dodt Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy. PLoS ONE |
| title | Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy. |
| title_full | Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy. |
| title_fullStr | Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy. |
| title_full_unstemmed | Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy. |
| title_short | Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy. |
| title_sort | cerebral β amyloidosis in mice investigated by ultramicroscopy |
| url | http://europepmc.org/articles/PMC4446269?pdf=render |
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