Role of membrane biophysics in Alzheimer's–related cell pathways

Abstract

Cellular membrane alterations are commonly observed in many diseases, including Alzheimer's disease (AD). Membrane biophysical properties, such as membrane molecular order, membrane fluidity, organization of lipid rafts, and adhesion between membrane and cytoskeleton, play an important role in various cellular activities and functions. While membrane biophysics impacts a broad range of cellular pathways, this review addresses the role of membrane biophysics in amyloid-β peptide aggregation, Aβ-induced oxidative pathways, amyloid precursor protein processing, and cerebral endothelial functions in AD. Understanding the mechanism(s) underlying the effects of cell membrane properties on cellular processes should shed light on the development of new preventive and therapeutic strategies for this devastating disease.

Stability of Aβ‐fibril fragments in the presence of fatty acids

“…Examples are glycolipid‐rich Golgi membranes that induce formation of oligomer but not of fibrils; and lipid rafts isolated from brain tissue result only in the assembly of tetramers . Fatty acids also have significant effects on Alzheimer patient brains, and even nanomolar concentrations of Aβ can form pathological aggregates in vivo that are not observed in vitro . Hence, one could hypothesize that lipid and fatty acid interfaces encourage the formation of self‐replicating and self‐propagating Aβ‐assemblies, which finally lead to the specific fibril structures observed in patient brains.…”

“…18 Fatty acids also have significant effects on Alzheimer patient brains, 20 and even nanomolar concentrations of Aβ can form pathological aggregates in vivo that are not observed in vitro. 21,22 Hence, one could hypothesize that lipid and fatty acid interfaces encourage the formation of self-replicating and self-propagating Aβ-assemblies, which finally lead to the specific fibril structures observed in patient brains. This hypothesis is supported by the observation of prion-like self-propagating large fatty acid-derived oligomers (LFAOs), generated in the presence of lauric acid and stable after removal of the fatty acids, that in mice are causing cerebral amyloid angiopathy (a common copathology in Alzheimer's disease patients).…”

Stability of Aβ-fibril fragments in the presence of fatty acids

“…Examples are glycolipid-rich Golgi membranes that induce formation of oligomer but not of fibrils 17 ; and lipid rafts isolated from brain tissue result only in the assembly of tetramers 16 . Fatty acids also have significant effects on Alzheimer patient brains 18 , and even nanomolar concentrations of Aβ can form pathological aggregates in vivo that are not observed in vitro 19,20 . Hence, one could hypothesize that lipid and fatty acid interfaces encourage the formation of self-replicating and self-propagating Ab-assemblies, which finally lead to the unique fibril structures observed in patient brains.…”

Selective Fluidization of Synaptosomal Plasma Membrane Vesicles by 17β-Estradiol

“…The main point of the present study is that E2 exhibits a selective rather than nonselective fluidizing effect within Although the findings of this study cannot provide exact evidence for neuroprotection by E2, membrane fluidity can influence the dynamics of proteins and other biomolecules within the membrane, thereby affecting the functions of these molecules (Nicolson, 2014;Zhu et al, 2015). However, Fig.…”