Blood cholesterol levels are not consistently elevated in subjects with 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 long-term 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.
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Conference Article|
August 11 2014
Hypercholesterolaemia-induced oxidative stress at the blood–brain barrier
Irundika H.K. Dias;
Irundika H.K. Dias
*Life and Health Sciences and Aston Research Centre for Healthy Ageing, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.
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Maria C. Polidori;
Maria C. Polidori
†Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
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Helen R. Griffiths
Helen R. Griffiths
1
*Life and Health Sciences and Aston Research Centre for Healthy Ageing, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.
1To whom correspondence should be addressed (emailh.r.griffiths@aston.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 04 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 1001–1005.
Article history
Received:
June 04 2014
Citation
Irundika H.K. Dias, Maria C. Polidori, Helen R. Griffiths; Hypercholesterolaemia-induced oxidative stress at the blood–brain barrier. Biochem Soc Trans 1 August 2014; 42 (4): 1001–1005. doi: https://doi.org/10.1042/BST20140164
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