title: Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier.
abstract: 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.
authors.affiliation: *Life and Health Sciences and Aston Research Centre for Healthy Ageing, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.
authors.forename: Irundika H K
authors.initials: IH
authors.lastname: Dias
authors.affiliation: †Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Polidori
authors.affiliation: *Life and Health Sciences and Aston Research Centre for Healthy Ageing, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Griffiths
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors