Altered synaptic structure in the hippocampus in a mouse model of Alzheimer's disease with soluble amyloid-ß oligomers and no plaque pathology.
Mol Neurodegener
; 9: 41, 2014 Oct 13.
Article
em En
| MEDLINE
| ID: mdl-25312309
ABSTRACT
BACKGROUND:
Mounting evidence suggests that soluble oligomers of amyloid-ß (oAß) represent the pertinent synaptotoxic form of Aß in sporadic Alzheimer's disease (AD); however, the mechanistic links between oAß and synaptic degeneration remain elusive. Most in vivo experiments to date have been limited to examining the toxicity of oAß in mouse models that also possess insoluble fibrillar Aß (fAß), and data generated from these models can lead to ambiguous interpretations. Our goal in the present study was to examine the effects of soluble oAß on neuronal and synaptic structure in the amyloid precursor protein (APP) E693Q ("Dutch") mouse model of AD, which develops intraneuronal accumulation of soluble oAß with no detectable plaques in AD-relevant brain regions. We performed quantitative analyses of neuronal pathology, including dendrite morphology, spine density, and synapse ultrastructure in individual hippocampal CA1 neurons.RESULTS:
When assessing neuronal morphology and complexity we observed significant alterations in apical but not in basal dendritic arbor length in Dutch mice compared to wild type. Moreover, Dutch mice exhibited a significant decrease in dendritic arborization with a decrease in dendritic length and number of intersections at 120 µm and 150 µm from the soma, respectively. We next examined synaptic parameters and found that while there were no differences in overall synaptic structure, Dutch mice displayed a significant reduction in the post-synaptic density (PSD) length of synapses on mushroom spines, in comparison to wild type littermates.CONCLUSION:
The structural alterations to individual neurons in Dutch mice along with the changes in larger dendritic spines support the Aß oligomer hypothesis, which postulates that the early cognitive impairments that occur in AD are attributed to the accumulation of soluble oAß first affecting at the synaptic level with subsequent structural disturbances and cellular degeneration.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Peptídeos beta-Amiloides
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Doença de Alzheimer
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Hipocampo
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Neurodegener
Ano de publicação:
2014
Tipo de documento:
Article