Susanne Kilian - Academia.edu (original) (raw)
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Papers by Susanne Kilian
For retrieval of memories a minimum number of synapses representing parts of the information is n... more For retrieval of memories a minimum number of synapses representing parts of the information is necessary. The dementia Morbus Alzheimer is characterized by progressive dysfunction and loss of synapses. Therefore, the central issue in understanding the genesis of the disease is the search for the underlying reasons of both. As the APP protein plays a central role in the pathogenesis of AD, the goal of this work was to elucidate the contributions of APP in synapse function in the hippocampus, the brain region that is predominantly affected by Alzheimer´s Disease. Investigation of gene-targeted mice that expressed different truncations of APP, partly on an APLP2 knock-out background, allowed me to study the functions of the three major domains of APP in an in vivo system with physiological concentrations and processing of APP. All experiments were performed on the CA3-CA1 synapse in the mouse hippocampus by analysis of field recordings under various stimulus paradigms. Mice lacking AP...
The Journal of Neuroscience, 2007
It is well established that the proteolytic processing of the β-amyloid precursor protein (APP) g... more It is well established that the proteolytic processing of the β-amyloid precursor protein (APP) generates β-amyloid (Aβ), which plays a central role in the pathogenesis of Alzheimer's disease (AD). In contrast, the physiological role of APP and of its numerous proteolytic fragments and the question of whether a loss of these functions contributes to AD are still unknown. To address this question, we replaced the endogenous APP locus by gene-targeted alleles and generated two lines of knock-in mice that exclusively express APP deletion variants corresponding either to the secreted APP ectodomain (APPsα) or to a C-terminal (CT) truncation lacking the YENPTY interaction motif (APPΔCT15). Interestingly, the ΔCT15 deletion resulted in reduced turnover of holoAPP, increased cell surface expression, and strongly reduced Aβ levels in brain, likely because of reduced processing in the endocytic pathway. Most importantly, we demonstrate that in both APP knock-in lines the expression of AP...
For retrieval of memories a minimum number of synapses representing parts of the information is n... more For retrieval of memories a minimum number of synapses representing parts of the information is necessary. The dementia Morbus Alzheimer is characterized by progressive dysfunction and loss of synapses. Therefore, the central issue in understanding the genesis of the disease is the search for the underlying reasons of both. As the APP protein plays a central role in the pathogenesis of AD, the goal of this work was to elucidate the contributions of APP in synapse function in the hippocampus, the brain region that is predominantly affected by Alzheimer´s Disease. Investigation of gene-targeted mice that expressed different truncations of APP, partly on an APLP2 knock-out background, allowed me to study the functions of the three major domains of APP in an in vivo system with physiological concentrations and processing of APP. All experiments were performed on the CA3-CA1 synapse in the mouse hippocampus by analysis of field recordings under various stimulus paradigms. Mice lacking AP...
The Journal of Neuroscience, 2007
It is well established that the proteolytic processing of the β-amyloid precursor protein (APP) g... more It is well established that the proteolytic processing of the β-amyloid precursor protein (APP) generates β-amyloid (Aβ), which plays a central role in the pathogenesis of Alzheimer's disease (AD). In contrast, the physiological role of APP and of its numerous proteolytic fragments and the question of whether a loss of these functions contributes to AD are still unknown. To address this question, we replaced the endogenous APP locus by gene-targeted alleles and generated two lines of knock-in mice that exclusively express APP deletion variants corresponding either to the secreted APP ectodomain (APPsα) or to a C-terminal (CT) truncation lacking the YENPTY interaction motif (APPΔCT15). Interestingly, the ΔCT15 deletion resulted in reduced turnover of holoAPP, increased cell surface expression, and strongly reduced Aβ levels in brain, likely because of reduced processing in the endocytic pathway. Most importantly, we demonstrate that in both APP knock-in lines the expression of AP...