Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes.

Rebecca Piccarducci,Lucia Chico,Filippo Baldacci,Simona Daniele,Gabriele Siciliano,Ferdinando Franzoni,Jonathan Fusi,Claudia Martini,Ubaldo Bonuccelli

doi:10.3390/antiox8110538

Abstract

The allele epsilon 4 (ε4) of apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer’s disease (AD). ApoE protein plays a pivotal role in the synthesis and metabolism of amyloid beta (Aβ), the major component of the extracellular plaques that constitute AD pathological hallmarks. Regular exercise is an important preventive/therapeutic tool in aging and AD. Nevertheless, the impact of physical exercise on the well-being of erythrocytes, a good model of oxidative stress and neurodegenerative processes, remains to be investigated, particularly depending on ApoE polymorphism. Herein, we evaluate the oxidative status, Aβ levels, and the membrane’s composition of erythrocytes in a cohort of human subjects. In our hands, the plasma antioxidant capability (AOC), erythrocytes membrane fluidity, and the amount of phosphatidylcholine (PC) were demonstrated to be significantly decreased in the ApoE ε4 genotype and non-active subjects. In contrast, erythrocyte Aβ content and lipid peroxidation increased in ε4 carriers. Regular physical exercise was associated with an increased plasma AOC and membrane fluidity, as well as to a reduced amount of erythrocytes Aβ. Altogether, these data highlight the influence of the ApoE genotype on erythrocytes’ well-being and confirm the positive impact of regular physical exercise.

Highlights

The apolipoprotein E (ApoE) is a 299 amino acid glycoprotein encoded by the ApoE gene, and existing in three polymorphic alleles
In the central nervous system, ApoE is primarily released by astrocytes and is involved in cholesterol transport to neuronal cells via ApoE receptors [2]
In the last decades, ApoE protein has been demonstrated to play a pivotal role in synthesis and metabolism of amyloid beta (Aβ) [3], a protein identified as the major component of the Antioxidants 2019, 8, 538; doi:10.3390/antiox8110538

Summary

Introduction

The apolipoprotein E (ApoE) is a 299 amino acid glycoprotein encoded by the ApoE gene, and existing in three polymorphic alleles. ApoE isoform, ε2, ε3, and ε4, which present a global frequent of 8.4%, 77.7%, and 13.7%, respectively. These isoforms differ from each other for the amino acids at positions 112 and 158 that alter the structure and, subsequently, the function of each isoform [1,2]. ApoE mediates lipid transport and contributes to liver cholesterol metabolism in an isoform-dependent manner, and has been linked to hyperlipidemia and hypercholesterolemia [2,3]. In the central nervous system, ApoE is primarily released by astrocytes and is involved in cholesterol transport to neuronal cells via ApoE receptors [2]. In the last decades, ApoE protein has been demonstrated to play a pivotal role in synthesis and metabolism of amyloid beta (Aβ) [3], a protein identified as the major component of the Antioxidants 2019, 8, 538; doi:10.3390/antiox8110538 www.mdpi.com/journal/antioxidants

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