Novel amyloid-beta pathology C. elegans model reveals distinct neurons as seeds of pathogenicity.
Prog Neurobiol
; 198: 101907, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-32926945
ABSTRACT
Protein misfolding and aggregation are hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD). In AD, the accumulation and aggregation of tau and the amyloid-beta peptide Aß1-42 precedes the onset of AD symptoms. Modelling the aggregation of Aß is technically very challenging in vivo due to its size of only 42 aa. Here, we employed sub-stoichiometric labelling of Aß1-42 in C. elegans to enable tracking of the peptide in vivo, combined with the "native" aggregation of unlabeled Aß1-42. Expression of Aß1-42 leads to severe physiological defects, neuronal dysfunction and neurodegeneration. Moreover, we can demonstrate spreading of neuronal Aß to other tissues. Fluorescence lifetime imaging microscopy enabled a quantification of the formation of amyloid fibrils with ageing and revealed a heterogenic yet specific pattern of aggregation. Notably, we found that Aß aggregation starts in a subset of neurons of the anterior head ganglion, the six IL2 neurons. We further demonstrate that cell-specific, RNAi-mediated depletion of Aß in these IL2 neurons systemically delays Aß aggregation and pathology.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Prog Neurobiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha