Non-Fibrillar Oligomeric Amyloid-beta within Synapses
Alzheimer's disease (AD) is characterized by memory loss, insidious cognitive decline, profound neurodegeneration, and the extracellular accumulation of amyloid-beta (A beta) peptide in senile plaques and intracellular accumulation of tau in neurofibrillary tangles. Loss and dysfunction of syna...
| Autores: | , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p7510 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=7510 https://discovery.dundee.ac.uk/en/publications/non-fibrillar-oligomeric-amyloid-%CE%B2-within-synapses |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer's disease amyloid-beta array tomography synapses |
| Sumario: | Alzheimer's disease (AD) is characterized by memory loss, insidious cognitive decline, profound neurodegeneration, and the extracellular accumulation of amyloid-beta (A beta) peptide in senile plaques and intracellular accumulation of tau in neurofibrillary tangles. Loss and dysfunction of synapses are believed to underlie the devastating cognitive decline in AD. A large amount of evidence suggests that oligomeric forms of A beta associated with senile plaques are toxic to synapses, but the precise sub-synaptic localization of A beta and which forms are synaptotoxic remain unknown. Here, we characterize the sub-synaptic localization of A beta oligomers using three high-resolution imaging techniques, stochastic optical reconstruction microscopy, immunogold electron microscopy, and Forster resonance energy transfer in a plaque-bearing mouse model of AD. With all three techniques, we observe oligomeric A beta inside synaptic terminals. Further, we tested a panel of A beta antibodies using the relatively high-throughput array tomography technique to determine which forms are present in synapses. Our results show that different oligomeric A beta species are present in synapses and highlight the potential of array tomography for rapid testing of aggregation state specific A beta antibodies in brain tissue. |
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