biostudies-literatureIljina MAlzheimers Research UK28658https://www.ebi.ac.uk/biostudies/studies/S-EPMC4921824biostudies-literatureUnknown6Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer's disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to Scientific reportsQuantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms.PMC4921824ART-PhD2010-3Garcia GAIljina MDobson CMMichaels TCFlint JDear AJNarayan PFrenkel DKnowles TPKlenerman DfalseQuantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms.Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer's disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to 2016-01-01T00:00:00Z2016 Jun2025-04-04T14:04:48.403Z2019-03-27T02:16:58ZS-EPMC49218242734624710.1038/srep28658