This title appears in the Scientific Report :
2021
Please use the identifier:
http://hdl.handle.net/2128/27996 in citations.
Please use the identifier: http://dx.doi.org/10.3390/ijms22137062 in citations.
PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease
PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease
Understanding the physiopathology of Alzheimer’s disease (AD) has improved substantially based on studies of mouse models mimicking at least one aspect of the disease. Many transgenic lines have been established, leading to amyloidosis but lacking neurodegeneration. The aim of the current study was...
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Personal Name(s): | Camargo, Luana |
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Schöneck, Michael / Sangarapillai, Nivethini / Honold, Dominik / Shah, N. J. / Langen, Karl-Josef / Willbold, Dieter / Kutzsche, Janine / Schemmert, Sarah / Willuweit, Antje (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 Jülich-Aachen Research Alliance - Translational Brain Medicine; JARA-BRAIN Physik der Medizinischen Bildgebung; INM-4 |
Published in: | International journal of molecular sciences, 22 (2021) 13, S. 7062 - |
Imprint: |
Basel
Molecular Diversity Preservation International
2021
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DOI: |
10.3390/ijms22137062 |
Document Type: |
Journal Article |
Research Program: |
Brain Dysfunction and Plasticity |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.3390/ijms22137062 in citations.
Understanding the physiopathology of Alzheimer’s disease (AD) has improved substantially based on studies of mouse models mimicking at least one aspect of the disease. Many transgenic lines have been established, leading to amyloidosis but lacking neurodegeneration. The aim of the current study was to generate a novel mouse model that develops neuritic plaques containing the aggressive pyroglutamate modified amyloid-β (pEAβ) species in the brain. The TAPS line was developed by intercrossing of the pEAβ-producing TBA2.1 mice with the plaque-developing line APPswe/PS1ΔE9. The phenotype of the new mouse line was characterized using immunostaining, and different cognitive and general behavioral tests. In comparison to the parental lines, TAPS animals developed an earlier onset of pathology and increased plaque load, including striatal pEAβ-positive neuritic plaques, and enhanced neuroinflammation. In addition to abnormalities in general behavior, locomotion, and exploratory behavior, TAPS mice displayed cognitive deficits in a variety of tests that were most pronounced in the fear conditioning paradigm and in spatial learning in comparison to the parental lines. In conclusion, the combination of a pEAβ- and a plaque-developing mouse model led to an accelerated amyloid pathology and cognitive decline in TAPS mice, qualifying this line as a novel amyloidosis model for future studies. |