The Role of Lipid Domains and Physical Properties of Membranes in the Development of Age-Related Neurodegenerative Diseases

Krasnobaev, Vladimir D.; Batishchev, Oleg V.

doi:10.1134/s199074782209001x

Cited by 2 publications

(1 citation statement)

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“…We previously studied lipid rafts as formations with a certain boundary area and line tension (energy of the domain boundary per unit length of its perimeter) in a membrane [ 31 ]. We also investigated how molecules of various molecular geometry influence raft formation [ 32 , 33 ], acting as so-called line active components [ 34 ] and made an analysis of interplay between lipid domains and aging-related diseases [ 35 ]. Here, we used atomic force microscopy to investigate the interaction between the fragment APP 672–726 (corresponding to Aβ 1–55 ) and model membranes containing L o lipid domains with different concentrations of cholesterol for wild-type (WT) and L723P-mutant forms of APP.…”

Section: Introductionmentioning

confidence: 99%

Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content

Krasnobaev,

Bershatsky,

Bocharova

et al. 2023

Membranes

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One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid beta (Aβ) peptides in the brain. The processing of amyloid precursor protein (APP) into Aβ is dependent on the location of APP in the membrane, membrane lipid composition and, possibly, presence of lipid rafts. In this study, we used atomic force microscopy (AFM) to investigate the interaction between transmembrane fragment APP672–726 (corresponding to Aβ1–55) and its amyloidogenic mutant L723P with membranes combining liquid-ordered and liquid-disordered lipid phases. Our results demonstrated that most of the APP672–726 is located either in the liquid-disordered phase or at the boundary between ordered and disordered phases, and hardly ever in rafts. We did not notice any major changes in the domain structure induced by APP672–726. In membranes without cholesterol APP672–726, and especially its amyloidogenic mutant L723P formed annular structures and clusters rising above the membrane. Presence of cholesterol led to the appearance of concave membrane regions up to 2 nm in depth that were deeper for wild type APP672–726. Thus, membrane cholesterol regulates changes in membrane structure and permeability induced by APP that might be connected with further formation of membrane pores.

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