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<p>For more than a century, hypercholesterolemia has been linked to atherosclerotic cardiovascular disease. Notably, this metabolic condition has also been pointed out as a risk factor for neurodegenerative diseases, such as Alzheimer’s disease (AD). Oxidative stress seems to be the connective factor between hypercholesterolemia and cardio and neurological disorders. By disturbing redox homeostasis, hypercholesterolemia impairs nitric oxide (NO) availability, an essential vasoprotective element, and jeopardizes endothelial function and selective permeability. The central nervous system (CNS) is partially protected from peripheral insults due to an arrangement between endothelial cells, astrocytes, microglia, and pericytes that form the blood–brain barrier (BBB). The endothelial dysfunction related to hypercholesterolemia increases the risk of developing cardiovascular diseases and also initiates BBB breakdown, which is a cause of brain damage characterized by neuroinflammation, oxidative stress, mitochondrial dysfunction, and, ultimately, neuronal and synaptic impairment. In this regard, we reviewed the mechanisms by which hypercholesterolemia-induced oxidative stress affects peripheral vessels, BBB, and leads to memory deficits. Finally, we suggest oxidative stress as the missing link between hypercholesterolemia and dementia.</p>

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Hypercholesterolemia, oxidative stress, and low-grade inflammation: a potentially dangerous scenario to blood–brain barrier

  • 期刊论文

  • 发表日期：

    2025年5月17日

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  • Hémelin Resende Farias,
  • Lílian Corrêa Costa-Beber,
  • Fátima Theresinha Costa Rodrigues Guma,
  • Jade de Oliveira

摘要

For more than a century, hypercholesterolemia has been linked to atherosclerotic cardiovascular disease. Notably, this metabolic condition has also been pointed out as a risk factor for neurodegenerative diseases, such as Alzheimer’s disease (AD). Oxidative stress seems to be the connective factor between hypercholesterolemia and cardio and neurological disorders. By disturbing redox homeostasis, hypercholesterolemia impairs nitric oxide (NO) availability, an essential vasoprotective element, and jeopardizes endothelial function and selective permeability. The central nervous system (CNS) is partially protected from peripheral insults due to an arrangement between endothelial cells, astrocytes, microglia, and pericytes that form the blood–brain barrier (BBB). The endothelial dysfunction related to hypercholesterolemia increases the risk of developing cardiovascular diseases and also initiates BBB breakdown, which is a cause of brain damage characterized by neuroinflammation, oxidative stress, mitochondrial dysfunction, and, ultimately, neuronal and synaptic impairment. In this regard, we reviewed the mechanisms by which hypercholesterolemia-induced oxidative stress affects peripheral vessels, BBB, and leads to memory deficits. Finally, we suggest oxidative stress as the missing link between hypercholesterolemia and dementia.