Journal
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
Volume 48, Issue 8, Pages 813-824Publisher
SPRINGER
DOI: 10.1007/s00249-019-01407-x
Keywords
Amyloid-beta peptides; Molecular dynamics; Alzheimer disease; Polyunsaturated fatty acids; Lipid bilayers; Phospholipids; Omega-3
Categories
Funding
- Stockholm University
- Swedish Research Council (Vetenskapsrade t) [2017-03950]
- Swedish Research Council [2017-03950] Funding Source: Swedish Research Council
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Aggregation of amyloid-beta (A ss) peptides, cleaved from the amyloid precursor protein, is known as a precursor of the Alzheimer's disease (AD). It is also known that Alzheimer's disease is characterized by a substantial decrease of the amount of polyunsaturated lipids in the neuronal membranes of the frontal gray matter. To get insight into possible interconnection of these phenomena, we have carried out molecular dynamics simulations of two fragments of A beta peptide, A beta(1-28) and A beta(26-40), in four different lipid bilayers: two monocomponent ones (14:0- 14:0 PC, 18:0-22:6 PC), and two bilayers containing mixtures of 18:0-18:0 PE, 22:6-22:6 PE, 16:0-16:0 PC and 18:1-18:1 PC lipids of composition mimicking neuronal membranes in a healthy and AD brain. The simulations showed that the presence of lipids with highly unsaturated 22:6cis fatty acids chains strongly affects the interaction of amyloid-beta peptides with lipid membranes. The polyunsaturated lipids cause stronger adsorption of A beta-peptides by the membrane and lead to weaker binding between peptides when the latter form aggregates. This difference in the behaviour observed in monocomponent bilayers is propagated in a similar fashion to the mixed membranes mimicking composition of neuronal membranes in healthy and AD brains, with healthy membrane having higher fraction of polyunsaturated lipids. Our simulations give strong indication that it can be physical-chemical background of the interconnection between amyloid fibrillization causing Alzheimer's disease, and content of polyunsaturated lipids in the neuronal membranes.
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