Abstract
Alzheimers disease is a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary tangles. Cholinergic dysfunction is also a main pathological feature of the disease. Nevertheless, the links between cholinergic dysfunction and neuropathological hallmarks of Alzheimers are still unknown. In the present study, we aimed to further investigate Tau aggregation in cholinergic systems, in a Tau transgenic mouse model. THY-Tau22 mice have recently been described as a novel model of Alzheimer – like Tau pathology without motor deficits. This strain presents an age-dependent development of Tau pathology leading to synaptic dysfunctions as well as learning and memory impairments. In the present work, we observed that Tau pathology differentially affects cerebral structures. Interestingly, early Tau pathology was observed in both hippocampus and basal forebrain. Moreover, some morphological as well as functional alterations of the septohippocampal pathway suggest a disconnection between these two key brain regions in Alzheimers disease. Finally, these data suggest that Tau pathology may participate in cholinergic degeneration.
Keywords: Acetylcholine, axonal transport, basal forebrain, neurofibrillary tangles, phosphorylation
Current Alzheimer Research
Title: Early Tau Pathology Involving the Septo-Hippocampal Pathway in a Tau Transgenic Model: Relevance to Alzheimers Disease
Volume: 6 Issue: 2
Author(s): Karim Belarbi, Katharina Schindowski, Sylvie Burnouf, Raphaelle Caillierez, Marie-Eve Grosjean, Dominique Demeyer, Malika Hamdane, Nicolas Sergeant, David Blum and Luc Buee
Affiliation:
Keywords: Acetylcholine, axonal transport, basal forebrain, neurofibrillary tangles, phosphorylation
Abstract: Alzheimers disease is a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary tangles. Cholinergic dysfunction is also a main pathological feature of the disease. Nevertheless, the links between cholinergic dysfunction and neuropathological hallmarks of Alzheimers are still unknown. In the present study, we aimed to further investigate Tau aggregation in cholinergic systems, in a Tau transgenic mouse model. THY-Tau22 mice have recently been described as a novel model of Alzheimer – like Tau pathology without motor deficits. This strain presents an age-dependent development of Tau pathology leading to synaptic dysfunctions as well as learning and memory impairments. In the present work, we observed that Tau pathology differentially affects cerebral structures. Interestingly, early Tau pathology was observed in both hippocampus and basal forebrain. Moreover, some morphological as well as functional alterations of the septohippocampal pathway suggest a disconnection between these two key brain regions in Alzheimers disease. Finally, these data suggest that Tau pathology may participate in cholinergic degeneration.
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Belarbi Karim, Schindowski Katharina, Burnouf Sylvie, Caillierez Raphaelle, Grosjean Marie-Eve, Demeyer Dominique, Hamdane Malika, Sergeant Nicolas, Blum David and Buee Luc, Early Tau Pathology Involving the Septo-Hippocampal Pathway in a Tau Transgenic Model: Relevance to Alzheimers Disease, Current Alzheimer Research 2009; 6 (2) . https://dx.doi.org/10.2174/156720509787602843
DOI https://dx.doi.org/10.2174/156720509787602843 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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