Identification of neurotoxic cross-linked amyloid-β dimers in the Alzheimer's brain

75Citations
Citations of this article
94Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The primary structure of canonical amyloid-β-protein was elucidated more than 30 years ago, yet the forms of amyloid-β that play a role in Alzheimer's disease pathogenesis remain poorly defined. Studies of Alzheimer's disease brain extracts suggest that amyloid-β, which migrates on sodium dodecyl sulphate polyacrylamide gel electrophoresis with a molecular weight of ∼7 kDa (7kDa-Aβ), 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-Aβ contains a heterogeneous mixture of covalently cross-linked dimers in the absence of any other detectable proteins. The identification of amyloid-β 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.

Cite

CITATION STYLE

APA

Brinkmalm, G., Hong, W., Wang, Z., Liu, W., O’Malley, T. T., Sun, X., … Walsh, D. M. (2019). Identification of neurotoxic cross-linked amyloid-β dimers in the Alzheimer’s brain. Brain, 142(5), 1441–1457. https://doi.org/10.1093/brain/awz066

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free