Cortical alterations of peptidergic secretion in Alzheimer's disease = Alteraciones corticales de la secreción peptidérgica en la enfermedad de Alzheimer
The Alzheimer’s disease is a disorder characterized by the presence of senile plaques and neurofibrillary tangles caused by the aberrant accumulation of β-amyloid peptide and hyperphosphorylated Tau, respectively. Nowadays, AD is the main cause of dementia, being aging its main risk factor. Given th...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/456816 |
| Acceso en línea: | http://hdl.handle.net/10803/456816 |
| Access Level: | acceso abierto |
| Palabra clave: | Malaltia d'Alzheimer Enfermedad de Alzheimer Alzheimer's disease Escorça cerebral Corteza cerebral Cerebral cortex Neurotransmissió Neurotransmisión Neural transmission Ciències Experimentlas i Matemàtiques 576 |
| Sumario: | The Alzheimer’s disease is a disorder characterized by the presence of senile plaques and neurofibrillary tangles caused by the aberrant accumulation of β-amyloid peptide and hyperphosphorylated Tau, respectively. Nowadays, AD is the main cause of dementia, being aging its main risk factor. Given that progressive alterations have been detected in neuropeptide levels in patients and animal models of Alzheimer's disease, it has been suggested that this pathway may be involved in the neurophysiology of the disease. In this doctoral thesis, we study the cortical alterations of the peptidergic secretion pathway in Alzheimer's disease. During its elaboration, the localization of dense granule proteins in the normal brain has been characterized and aberrant accumulations of these are found in the pathological structures typical of the disease, such as granulovacuolar degeneration bodies or dystrophic neurites. The study of the acute effect of β-amyloid peptide showed a reduction of the regulated peptidergic release in neurons and astrocytes in vitro as well as in acute brain slices in response to the treatment, suggesting that the secretion pathway can suppose an early target of the pathology. Finally, the content analysis of characteristic proteins of the pathway showed a reduction of their levels in the cerebrospinal fluid of transgenic animals and patients with mild cognitive impairment, which may suggest that the proteins of the route can be candidates as progression biomarkers to monitoring of the progression of Alzheimer's disease. |
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