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000842478 1001_ $$0P:(DE-Juel1)145867$$aDunkelmann, Tina$$b0
000842478 245__ $$aComprehensive characterization of the pyroglutamate Aβ induced motor neurodegenerative phenotype of TBA2.1 mice
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000842478 520__ $$aAlzheimer’s disease (AD) is the most common neurodegenerative disorder and is being intensively investigated using a broad variety of animal models. Many of these models express mutant versions of human amyloid-β protein precursor (AβPP) that are associated with amyloid-β protein (Aβ)-induced early onset familial AD. Most of these models, however, do not develop bold neurodegenerative pathology and the respective phenotypes. Nevertheless, this may well be essential for their suitability to identify therapeutically active compounds that have the potential for a curative or at least disease-modifying therapy in humans. In this study, the new transgenic mouse model TBA2.1 was explored in detail to increase knowledge about the neurodegenerative process induced by the presence of pyroglutamate modified human Aβ3-42 (pEAβ3-42). Analysis of the sensorimotor phenotype, motor coordination, Aβ pathology, neurodegeneration, and gliosis revealed formation and progression of severe pathology and phenotypes including massive neuronal loss in homozygous TBA2.1 mice within a few months. In contrast, the start of a slight phenotype was observed only after 21 months in heterozygous mice. These data highlight the role of pEAβ3-42 in the disease development and progression of AD. Based on the findings of this study, homozygous TBA2.1 mice can be utilized to gain deeper understanding in the underlying mechanisms of pEAβ3-42 and might be suitable as an animal model for treatment studies targeting toxic Aβ species, complementary to the well described transgenic AβPP mouse models.
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000842478 7001_ $$0P:(DE-Juel1)165908$$aSchemmert, Sarah$$b1$$ufzj
000842478 7001_ $$0P:(DE-HGF)0$$aHonold, Dominik$$b2
000842478 7001_ $$0P:(DE-Juel1)164429$$aTeichmann, Kerstin$$b3
000842478 7001_ $$0P:(DE-HGF)0$$aButzküven, Elke$$b4
000842478 7001_ $$0P:(DE-HGF)0$$aDemuth, Hans-Ulrich$$b5
000842478 7001_ $$0P:(DE-Juel1)131794$$aShah, N. J.$$b6$$ufzj
000842478 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b7$$ufzj
000842478 7001_ $$0P:(DE-Juel1)159137$$aKutzsche, Janine$$b8$$ufzj
000842478 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b9$$eCorresponding author$$ufzj
000842478 7001_ $$0P:(DE-Juel1)144347$$aWilluweit, Antje$$b10$$eCorresponding author$$ufzj
000842478 773__ $$0PERI:(DE-600)2070772-1$$a10.3233/JAD-170775$$n1$$p115-130$$tJournal of Alzheimer's disease$$v63$$x1387-2877$$y2018
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