Do APOE4, malnutrition, and long COVID-19 compound the risk factors for stroke in adverse environments?
Year: 2024
Type: article
Abstract: APOE, malnutrition, long COVID, stroke, adverse environment APOE under adverse environmentsApolipoprotein E (apoE) is a 299 amino acid protein with vital functions in transporting plasma cholesterol from peripheral tissues to the liver to be metabolized (1).The human apolipoprotein E gene (APOE) is polymorphic, carrying three common alleles that encode distinct apoE isoforms (apoE4, apoE3, and apoE2), displaying differing biological functions and binding affinities to LDL receptors.ApoE4 is primarily expressed in the liver, functioning as a ligand during the receptor-mediated endocytosis of lipoprotein particles (2, 3), resulting in increased total cholesterol and LDL levels, whereas apoE2 has opposite effects (4).ApoE4 has immunomodulatory roles in different experimental models (5, 6) and may have distinct effects under adverse and privileged environments.In the CNS, apoE is the primary apolipoprotein regulating lipid metabolism, being mainly produced by astrocytes.ApoE is involved in brain cholesterol recycling and redistribution, affecting membrane maintenance, organelle biogenesis, and synaptogenesis, which are essential for neuroplasticity (7).ApoE4 is highly expressed in glial cells and is recognized to bind to brain amyloid plaques and is a culprit of unbalanced neuroinflammatory responses in Alzheimer's disease (AD) patients and declining health status (8).APOE4 carriers have a significantly increased risk of acquiring late-onset Alzheimer's and cardiovascular diseases (9).Following cerebral focal ischemia, apoE4 was found to exacerbate infarction size and hemiparesis in transgenic mice, as well as increased peri-infarct GFAP-associated reactive astrocytosis when compared to apoE3 and apoE2 (10,11).Although much is known about how apoE-cholesterol-derived from astrocytes affects the build-up of synaptic circuits (12) and impairment in AD (the latter according to apoE2 < apoE3 < apoE4) (13), a gap of knowledge remains on apoE role on brain synapses following stroke under adverse environments.Despite the adverse effects of APOE4 in modern Western societies, the prevalence of APOE4, considered the ancestral APOE allele, is higher in hunter-gatherer remote populations (4).A reason for APOE4 prevalence in populations with less access to health services may be the high exposure to endemic infectious pathogens (14).APOE4
Source: Frontiers in Nutrition
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4400914636