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@ARTICLE{Dunkelmann:842478,
author = {Dunkelmann, Tina and Schemmert, Sarah and Honold, Dominik
and Teichmann, Kerstin and Butzküven, Elke and Demuth,
Hans-Ulrich and Shah, N. J. and Langen, Karl-Josef and
Kutzsche, Janine and Willbold, Dieter and Willuweit, Antje},
title = {{C}omprehensive characterization of the pyroglutamate {A}β
induced motor neurodegenerative phenotype of {TBA}2.1 mice},
journal = {Journal of Alzheimer's disease},
volume = {63},
number = {1},
issn = {1387-2877},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {FZJ-2018-00703},
pages = {115-130},
year = {2018},
abstract = {Alzheimer’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.},
cin = {ICS-6 / INM-4 / JARA-BRAIN / INM-11},
ddc = {610},
cid = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)INM-4-20090406 /
$I:(DE-82)080010_20140620$ / I:(DE-Juel1)INM-11-20170113},
pnm = {573 - Neuroimaging (POF3-573) / 553 - Physical Basis of
Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-573 / G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29578479},
UT = {WOS:000430016100011},
doi = {10.3233/JAD-170775},
url = {https://juser.fz-juelich.de/record/842478},
}