A Kinetic Map of the Influence of Biomimetic Lipid Model Membranes on Aβ42 Aggregation

Kevin N. Baumann, Greta Šneiderienė, Michele Sanguanini, Matthias Schneider, Oded Rimon, Alicia González Díaz, Heather Greer, Dev Thacker, Sara Linse, Tuomas P.J. Knowles, Michele Vendruscolo

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


The aggregation of the amyloid β (Aβ) peptide is one of the molecular hallmarks of Alzheimer’s disease (AD). Although Aβ deposits have mostly been observed extracellularly, various studies have also reported the presence of intracellular Aβ assemblies. Because these intracellular Aβ aggregates might play a role in the onset and progression of AD, it is important to investigate their possible origins at different locations of the cell along the secretory pathway of the amyloid precursor protein, from which Aβ is derived by proteolytic cleavage. Senile plaques found in AD are largely composed of the 42-residue form of Aβ (Aβ42). Intracellularly, Aβ42 is produced in the endoplasmatic reticulum (ER) and Golgi apparatus. Since lipid bilayers have been shown to promote the aggregation of Aβ, in this study, we measure the effects of the lipid membrane composition on the in vitro aggregation kinetics of Aβ42. By using large unilamellar vesicles to model cellular membranes at different locations, including the inner and outer leaflets of the plasma membrane, late endosomes, the ER, and the Golgi apparatus, we show that Aβ42 aggregation is inhibited by the ER and Golgi model membranes. These results provide a preliminary map of the possible effects of the membrane composition in different cellular locations on Aβ aggregation and suggest the presence of an evolutionary optimization of the lipid composition to prevent the intracellular aggregation of Aβ.

Sidor (från-till)323-329
Antal sidor7
TidskriftACS Chemical Neuroscience
StatusPublished - 2023 jan. 18

Ämnesklassifikation (UKÄ)

  • Biokemi och molekylärbiologi


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