1,721,117 research outputs found
Altered neurogenesis in mouse models of Alzheimer disease
No full textAmyloid-β (Aβ) peptides, as well as a variety of other protein fragments, are derived from proteolytical cleavage of the amyloid precursor protein (APP) and have been demonstrated to play a key role in the pathological changes underlying Alzheimer disease (AD). In AD mouse models, altered neurogenesis has been repeatedly reported to be associated with further AD-typical pathological hallmarks such as extracellular plaque deposition, behavioral deficits or neuroinflammation. While a toxic role of Aβ in neurodegeneration and impaired neuronal progenitor proliferation is likely and well-accepted, recent findings also suggest an important influence of APP-derived proteolitical fragments like the APP intracellular domain (AICD), as well as of APP itself
Extraction of Soluble and Insoluble Protein Fractions from Mouse Brains and Spinal Cords
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Endogenous Apolipoprotein E (ApoE) Fragmentation Is Linked to Amyloid Pathology in Transgenic Mouse Models of Alzheimer’s Disease
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Physical activity and cognitive stimulation ameliorate learning and motor deficits in a transgenic mouse model of Alzheimer’s disease
No full textThe modified amyloid hypothesis of Alzheimer dementia - intraneuronal Abeta induces neurodegeneration
No full textThe present short review recapitulates the molecular pathology of Alzheimer's disease and discusses the most important animal models and current treatment strategies. The currently approved and only mildly efficient drugs treat only symptoms. Genetical, neuropathological and biochemical data support the importance of the amyloid hypothesis of Alzheimer's disease, which is at the moment the most influential hypothesis. The resulting research approaches have disease-modifying potential. At the basis of the amlyloid hypothesis many treatment strategies have been performed, which were markedly successful in preclinical animal models. However, the treatment success in Alzheimer patients is unfortunately still lacking. This could be due to the used animal models showing mostly only marginal behavioural deficits and no Alzheimer-like nerve cell loss, although they all developed a more or less pronounced plaque load. We know however today, that Alzheimer plaques are not mainly responsible for the cell loss. Therefore novel animal models have been developed that show early intraneuronal A beta accumulation, massive neuron loss and robust behavioural deficits. A successful treatment of an animal model with such a phenotype would be very likely better suited to be transferred into the clinic. The final validation or falsification of distinct Alzheimer hypotheses and the resulting treatment strategies will be obtained however only after clinical proof
Intraneuronal A beta accumulation and neurodegeneration: Lessons from transgenic models
No full textAims: In the present review we summarize current knowledge on the concept of intraneuronal A beta as a determinant for neuron loss and other pathological alterations in transgenic models for Alzheimer disease. Main methods: We discuss the use of transgenic mouse and non-vertebrate transgenic models accumulating intracellular A beta peptides and their impact on the ongoing discussion. Key findings: Intraneuronal A beta accumulation in transgenic models is intimately linked to pathological alterations including neuron loss. One of the technical caveats for visualizing intraneuronal A beta is the antibody used to unequivocally demonstrate its presence. Very often antibodies were used that recognize both A beta and APP, leading to false positive results due to misinterpretation. Significance: Whereas a clear relationship between intraneuronal A beta accumulation and neuron loss is evident in transgenic mouse models it remains an unresolved issue whether the concept of intraneuronal A beta can be integrated into the human pathology as well. (C) 2012 Elsevier Inc. All rights reserved
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