@article{discovery10145146,
            year = {2022},
          volume = {13},
          number = {8},
           title = {Amyloid-{\ensuremath{\beta}} peptide 37, 38 and 40 individually and cooperatively inhibit amyloid-{\ensuremath{\beta}} 42 aggregation},
           month = {February},
         journal = {Chemical Science},
           pages = {2423--2439},
            note = {{\copyright} Royal Society of Chemistry 2022. Original content in this article is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/).},
       publisher = {ROYAL SOC CHEMISTRY},
        abstract = {The pathology of Alzheimer's disease is connected to the aggregation of {\ensuremath{\beta}}-amyloid (A{\ensuremath{\beta}}) peptide, which in vivo exists as a number of length-variants. Truncations and extensions are found at both the N- and C-termini, relative to the most commonly studied 40- and 42-residue alloforms. Here, we investigate the aggregation of two physiologically abundant alloforms, A{\ensuremath{\beta}}37 and A{\ensuremath{\beta}}38, as pure peptides and in mixtures with A{\ensuremath{\beta}}40 and A{\ensuremath{\beta}}42. A variety of molar ratios were applied in quaternary mixtures to investigate whether a certain ratio is maximally inhibiting of the more toxic alloform A{\ensuremath{\beta}}42. Through kinetic analysis, we show that both A{\ensuremath{\beta}}37 and A{\ensuremath{\beta}}38 self-assemble through an autocatalytic secondary nucleation reaction to form fibrillar {\ensuremath{\beta}}-sheet-rich aggregates, albeit on a longer timescale than A{\ensuremath{\beta}}40 or A{\ensuremath{\beta}}42. Additionally, we show that the shorter alloforms co-aggregate with A{\ensuremath{\beta}}40, affecting both the kinetics of aggregation and the resulting fibrillar ultrastructure. In contrast, neither A{\ensuremath{\beta}}37 nor A{\ensuremath{\beta}}38 forms co-aggregates with A{\ensuremath{\beta}}42; however, both short alloforms reduce the rate of A{\ensuremath{\beta}}42 aggregation in a concentration-dependent manner. Finally, we show that the aggregation of A{\ensuremath{\beta}}42 is more significantly impeded by a combination of A{\ensuremath{\beta}}37, A{\ensuremath{\beta}}38, and A{\ensuremath{\beta}}40 than by any of these alloforms independently. These results demonstrate that the aggregation of any given A{\ensuremath{\beta}} alloform is significantly perturbed by the presence of other alloforms, particularly in heterogeneous mixtures, such as is found in the extracellular fluid of the brain. This journal is},
             url = {https://doi.org/10.1039/D1SC02990H},
          author = {Braun, Gabriel A and Dear, Alexander J and Sanagavarapu, Kalyani and Zetterberg, Henrik and Linse, Sara}
}