Nature of the amyloid-beta monomer and the monomer-oligomer equilibrium

Nag, Suman, Sarkar, Bidyut, Banerjee, Arkarup, Sahoo, Bankanidhi, Sreenivasan, Varun K A, Kombrabail, Mamata, Mralidharan, Chandrakesan, Maiti, Sudipta (April 2011) Nature of the amyloid-beta monomer and the monomer-oligomer equilibrium. Journal of Biological Chemistry, 286 (16). pp. 13827-13833. ISSN 0021-9258

DOI: 10.1074/jbc.M110.199885


The monomer to oligomer transition initiates the aggregation and pathogenic transformation of Alzheimer amyloid-β (Aβ) peptide. However, the monomeric state of this aggregation-prone peptide has remained beyond the reach of most experimental techniques, and a quantitative understanding of this transition is yet to emerge. Here, we employ single-molecule level fluorescence tools to characterize the monomeric state and the monomer-oligomer transition at physiological concentrations in buffers mimicking the cerebrospinal fluid (CSF). Our measurements show that the monomer has a hydrodynamic radius of 0.9 ± 0.1 nm, which confirms the prediction made by some of the in silico studies. Surprisingly, at equilibrium, both Aβ40 and Aβ42 remain predominantly monomeric up to 3 μM, above which it forms large aggregates. This concentration is much higher than the estimated concentrations in the CSF of either normal or diseased brains. If Aβ oligomers are present in the CSF and are the key agents in Alzheimer pathology, as is generally believed, then these must be released in the CSF as preformed entities. Although the oligomers are thermodynamically unstable, we find that a large kinetic barrier, which is mostly entropic in origin, strongly impedes their dissociation. Thermodynamic principles therefore allow the development of a pharmacological agent that can catalytically convert metastable oligomers into nontoxic monomers.

Item Type: Paper
CSHL Authors:
Communities: CSHL labs > Banerjee lab
Depositing User: Matthew Dunn
Date: 22 April 2011
Date Deposited: 30 Nov 2020 21:28
Last Modified: 30 Nov 2020 21:28
PMCID: PMC3077583
Related URLs:

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving