Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier

Irundika H.K. Dias; Maria C. Polidori; Helen R. Griffiths

doi:10.1042/BST20140164

Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier

Irundika H.K. Dias, Maria C. Polidori, Helen R. Griffiths^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Blood cholesterol levels are not consistently elevated in subjectswith age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased longterm risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood-brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life. © The Authors Journal compilation © 2014 Biochemical Society.

Original language	English
Pages (from-to)	1001-1005
Number of pages	5
Journal	Biochemical Society Transactions
Volume	42
Issue number	4
DOIs	https://doi.org/10.1042/BST20140164
Publication status	Published - Aug 2014

Bibliographical note

© the Biochemical Society.

Provided the original publication of the article, or portion of the article, is properly cited, Authors retain the following non-exclusive rights:

1.To reproduce their article in whole or in part in any printed volume (book or thesis) of which they are the Author or Editor
2.To reproduce their article in whole or in part at the Author's current academic institution for teaching purposes
3.To reuse figures, tables, illustrations or photos from the article in commercial or non-commercial works created by them
4.To post a copy of the Immediate Publication (i.e. the Accepted Manuscript*) at the Author's Institutional Repository, 6 months after publication, provided that this is linked to the article on the journal website (e.g. through the DOI).

Keywords

alzheimer's disease
blood-brain barrier
liver X receptor (LXR)
low-density lipoprotein (LDL)
oxidative stress
oxysterol
statin

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10.1042/BST20140164

Hypercholesterolaemia-induced oxidative stress on blood brain barrier
© the Biochemical Society. Provided the original publication of the article, or portion of the article, is properly cited, Authors retain the following non-exclusive rights: 1.To reproduce their article in whole or in part in any printed volume (book or thesis) of which they are the Author or Editor 2.To reproduce their article in whole or in part at the Author's current academic institution for teaching purposes 3.To reuse figures, tables, illustrations or photos from the article in commercial or non-commercial works created by them 4.To post a copy of the Immediate Publication (i.e. the Accepted Manuscript*) at the Author's Institutional Repository, 6 months after publication, provided that this is linked to the article on the journal website (e.g. through the DOI).
Accepted author manuscript, 55.3 KB

http://www.biochemsoctrans.org/bst/042/bst0421001.htm

Cite this

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title = "Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier",

abstract = "Blood cholesterol levels are not consistently elevated in subjectswith age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased longterm risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood-brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life. {\textcopyright} The Authors Journal compilation {\textcopyright} 2014 Biochemical Society.",

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Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier

Abstract

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Keywords

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