Identification of neurotoxic cross-linked amyloid-ß dimers in the Alzheimer's brain.
Brain
; 142(5): 1441-1457, 2019 05 01.
Article
em En
| MEDLINE
| ID: mdl-31032851
ABSTRACT
The primary structure of canonical amyloid-ß-protein was elucidated more than 30 years ago, yet the forms of amyloid-ß that play a role in Alzheimer's disease pathogenesis remain poorly defined. Studies of Alzheimer's disease brain extracts suggest that amyloid-ß, which migrates on sodium dodecyl sulphate polyacrylamide gel electrophoresis with a molecular weight of â¼7 kDa (7kDa-Aß), is particularly toxic; however, the nature of this species has been controversial. Using sophisticated mass spectrometry and sensitive assays of disease-relevant toxicity we show that brain-derived bioactive 7kDa-Aß contains a heterogeneous mixture of covalently cross-linked dimers in the absence of any other detectable proteins. The identification of amyloid-ß dimers may open a new phase of Alzheimer's research and allow a better understanding of Alzheimer's disease, and how to monitor and treat this devastating disorder. Future studies investigating the bioactivity of individual dimers cross-linked at known sites will be critical to this effort.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Peptídeos beta-Amiloides
/
Multimerização Proteica
/
Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
Limite:
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article