TY  - JOUR
AU  - Camargo, Luana
AU  - Schöneck, Michael
AU  - Sangarapillai, Nivethini
AU  - Honold, Dominik
AU  - Shah, N. J.
AU  - Langen, Karl-Josef
AU  - Willbold, Dieter
AU  - Kutzsche, Janine
AU  - Schemmert, Sarah
AU  - Willuweit, Antje
TI  - PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease
JO  - International journal of molecular sciences
VL  - 22
IS  - 13
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - FZJ-2021-02819
SP  - 7062 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 34209113
UR  - <Go to ISI:>//WOS:000671201600001
DO  - DOI:10.3390/ijms22137062
UR  - https://juser.fz-juelich.de/record/893764
ER  -