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Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.

Jährling N, Becker K, Wegenast-Braun BM, Grathwohl SA, Jucker M, Dodt HU - PLoS ONE (2015)

Bottom Line: Alzheimer´s disease (AD) is the most common neurodegenerative disorder.Ultramicroscopy makes this possible by replacing mechanical slicing in standard histology by optical sectioning.This in turn is the basis to study neural network degeneration upon cerebral β-amyloidosis and to assess Aβ-targeting therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioelectronics, FKE, Vienna University of Technology, Vienna, Austria; Section of Bioelectronics, Center for Brain Research (MUW), Vienna, Austria.

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.

No MeSH data available.


Related in: MedlinePlus

UM´s example images of APPPS1.Cross sections in the orthogonal directions are used to analyze the β-amyloid plaque distribution in the entire mouse brain of APPPS1. The β-amyloid plaques appear as bright dots in the neocortex (example of an animal of the young group is shown). A) Transversal plane (x,y); B) transversal plane (x,y); C) Computed sagittal plane (yz); D) computed coronal plane (xz). ctx: cortex; cb: cerebellum; hc: hippocampus, bs: brainstem; ob: olfactory bulb.
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pone.0125418.g002: UM´s example images of APPPS1.Cross sections in the orthogonal directions are used to analyze the β-amyloid plaque distribution in the entire mouse brain of APPPS1. The β-amyloid plaques appear as bright dots in the neocortex (example of an animal of the young group is shown). A) Transversal plane (x,y); B) transversal plane (x,y); C) Computed sagittal plane (yz); D) computed coronal plane (xz). ctx: cortex; cb: cerebellum; hc: hippocampus, bs: brainstem; ob: olfactory bulb.

Mentions: Via visual analysis of the single images of each stack, the β-amyloid plaque distribution was examined for each APPPS1 mouse brain. Fig 2 shows how the β-amyloid plaque distribution was recorded two dimensionally by optical sectioning. The young group shows modest β-amyloid deposition in the cortex and minor deposition in the hippocampal region. In contrast, robust β-amyloid deposition throughout almost the entire brain is observed in the adult mice. In accordance with earlier results [13], β-amyloid deposition in the cerebellum was less compared to other brain regions. It should be noted that structures deep within the brains of the adult animals were difficult to analyze, as these brains were not completely transparent.


Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy.

Jährling N, Becker K, Wegenast-Braun BM, Grathwohl SA, Jucker M, Dodt HU - PLoS ONE (2015)

UM´s example images of APPPS1.Cross sections in the orthogonal directions are used to analyze the β-amyloid plaque distribution in the entire mouse brain of APPPS1. The β-amyloid plaques appear as bright dots in the neocortex (example of an animal of the young group is shown). A) Transversal plane (x,y); B) transversal plane (x,y); C) Computed sagittal plane (yz); D) computed coronal plane (xz). ctx: cortex; cb: cerebellum; hc: hippocampus, bs: brainstem; ob: olfactory bulb.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4446269&req=5

pone.0125418.g002: UM´s example images of APPPS1.Cross sections in the orthogonal directions are used to analyze the β-amyloid plaque distribution in the entire mouse brain of APPPS1. The β-amyloid plaques appear as bright dots in the neocortex (example of an animal of the young group is shown). A) Transversal plane (x,y); B) transversal plane (x,y); C) Computed sagittal plane (yz); D) computed coronal plane (xz). ctx: cortex; cb: cerebellum; hc: hippocampus, bs: brainstem; ob: olfactory bulb.
Mentions: Via visual analysis of the single images of each stack, the β-amyloid plaque distribution was examined for each APPPS1 mouse brain. Fig 2 shows how the β-amyloid plaque distribution was recorded two dimensionally by optical sectioning. The young group shows modest β-amyloid deposition in the cortex and minor deposition in the hippocampal region. In contrast, robust β-amyloid deposition throughout almost the entire brain is observed in the adult mice. In accordance with earlier results [13], β-amyloid deposition in the cerebellum was less compared to other brain regions. It should be noted that structures deep within the brains of the adult animals were difficult to analyze, as these brains were not completely transparent.

Bottom Line: Alzheimer´s disease (AD) is the most common neurodegenerative disorder.Ultramicroscopy makes this possible by replacing mechanical slicing in standard histology by optical sectioning.This in turn is the basis to study neural network degeneration upon cerebral β-amyloidosis and to assess Aβ-targeting therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioelectronics, FKE, Vienna University of Technology, Vienna, Austria; Section of Bioelectronics, Center for Brain Research (MUW), Vienna, Austria.

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.

No MeSH data available.


Related in: MedlinePlus