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Cited by 1,044Cholesterol and Lipid MetabolismBarrier Structure and Function StudiesAlzheimer's disease research and treatments

The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.

Brain Cholesterol: Long Secret Life Behind a Barrier

Björkhem, Ingemar, Meaney, Steve·2004·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/01.atv.0000120374.59826.1b
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Abstract

Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Approximately 25% of the total amount of the cholesterol present in humans is localized to this organ, most of it present in myelin. Almost all brain cholesterol is a product of local synthesis, with the blood-brain barrier efficiently protecting it from exchange with lipoprotein cholesterol in the circulation. Thus, there is a highly efficient apolipoprotein-dependent recycling of cholesterol in the brain, with minimal losses to the circulation. Under steady-state conditions, most of the de novo synthesis of cholesterol in the brain appears to be balanced by excretion of the cytochrome P-450-generated oxysterol 24S-hydroxycholesterol. This oxysterol is capable of escaping the recycling mechanism and traversing the blood-brain barrier. Cholesterol levels and cholesterol turnover are affected in neurodegenerating disorders, and the capacity for cholesterol transport and recycling in the brain seems to be of importance for the development of such diseases. The possibility has been discussed that administration of inhibitors of cholesterol synthesis may reduce the prevalence of Alzheimer disease. No firm conclusions can, however, be drawn from the studies presented thus far. In the present review, the most recent advances in our understanding of cholesterol turnover in the brain is discussed.

Overview

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Crossref · 10.1161/01.atv.0000120374.59826.1b

Cites

112 of 112 references verified0 citation errors · 0 not checkable

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  • The adult brain relies on endogenous synthesis for its cholesterol needs because the blood-brain barrier is virtually impermeable to circulating lipoproteins and cholesterol molecules do not cross the blood-brain barrier.

    “The adult brain vastly relies on endogenous synthesis for its cholesterol needs since the BBB is virtually impermeable to circulating lipoproteins (52) and since, unlike oxysterols, cholesterol molecules do not cross the BBB (53).”

    From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [52]

  • Disruption of cholesterol homeostasis perturbs cell-autonomous and non-cell-autonomous functions, including inhibition of crucial signaling pathways and cellular crosstalk.

    “Disruption of cholesterol homeostasis has also been shown to perturb cell-autonomous and non-cell-autonomous functions, including inhibition of crucial signaling pathways and cellular crosstalk (Bjorkhem and Meaney, 2004; Martin et al., 2014).”

    From Sterol dysregulation in Smith–Lemli–Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk (2022) · cites this paper as Bjorkhem and Meaney, 2004

  • Cholesterol is essential for neurons, because a lack of cholesterol leads to synapse degeneration, impaired synaptic vesicle exocytosis and neurotransmission, and overall decreased neuronal activity.

    “Cholesterol is essential for neurons, because a lack of cholesterol leads to synapse degeneration, impaired synaptic vesicle exocytosis and neurotransmission, and overall decreased neuronal activity.[42][43][44]”

    From Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function (2024) · cites this paper as [42]

  • The most abundant brain lipids are cholesterol, ceramides, glucosyl ceramides, phosphatidylcholine, sphingomyelin, and sulfatides.

    “Out of all the brain lipids, the most abundant are cholesterol, ceramides, glucosyl ceramides, phosphatidylcholine, sphingomyelin, and sulfatides [61, 62].”

    From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [61]

Citations

Cites

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Research works printed but not linked: 6

  1. 1834, Annales de Chimie et de Physique, 56, 160
  2. Norton W. Isolation and characterisation of myelin. In: Bittman R ed. Cholesterol. New York: Plenum Press; 1998.
  3. 1996, J Mol Neurosci, 7, 29
  4. 2003, Pharmacopsychiatry, 36, 113
  5. 2002, Neurobiol Aging, 23, 273
  6. 2002, Front Biosci, 7, a50

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Metadata

Authors
Björkhem, I., & Meaney, S.
Affiliations
  • From the Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
  • Karolinska Institutet (SE)
ORCID
Meaney, Steve
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-05
Volume
24
Issue
5
Pages
806-815
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/01.atv.0000120374.59826.1b
OpenAlex
W2117842413
Cited by
1,044
References
112
Citations by year
2026: 50 · 2025: 51 · 2024: 56 · 2023: 77 · 2022: 63 · 2021: 62 · 2020: 66 · 2019: 56 · 2018: 39 · 2017: 43 · 2016: 45 · 2015: 51 · 2014: 41 · 2013: 38 · 2012: 44
FWCI
7.53
Type
journal article
Language
en
Open access
closed
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
brain cholesterol, cholesterol homeostasis, blood-brain barrier, myelin, de novo cholesterol synthesis, 24S-hydroxycholesterol, oxysterols, cytochrome P450, cholesterol turnover, neurodegenerative diseases, Alzheimer's disease, cholesterol biosynthesis inhibitors
MeSH terms
Animals, Blood-Brain Barrier, Brain, Cholesterol, Homeostasis, Humans, Hydroxycholesterols, Membrane Lipids, Myelin Sheath, Nerve Degeneration, Receptors, Cytoplasmic and Nuclear, Neuroprotective Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Rats

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