Comprehensive Characterization of the Pyroglutamate Amyloid-ß Induced Motor Neurodegenerative Phenotype of TBA2.1 Mice.
J Alzheimers Dis
; 63(1): 115-130, 2018.
Article
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| MEDLINE
| ID: mdl-29578479
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-ß protein precursor (AßPP) that are associated with amyloid-ß protein (Aß)-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 Aß3-42 (pEAß3-42). Analysis of the sensorimotor phenotype, motor coordination, Aß 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 pEAß3-42 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 pEAß3-42 and might be suitable as an animal model for treatment studies targeting toxic Aß species, complementary to the well described transgenic AßPP mouse models.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Enfermedades Neurodegenerativas
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Enfermedad de Alzheimer
/
Actividad Motora
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania