title: Impairment of the ABCA1 and SR-BI-mediated cholesterol efflux pathways and HDL anti-inflammatory activity in Alzheimer's disease.
abstract: The aim of our study was to investigate the effect of Alzheimer's disease (AD) on the cholesterol efflux capacity and anti-inflammatory activity of HDL. HDL and apoA-I were isolated from 20 healthy subjects and from 39 AD patients. Our results showed that serum- and HDL-mediated cholesterol efflux is significantly impaired in AD patients. This impairment of serum and HDL cholesterol efflux capacity was significantly inversely correlated to the AD severity as evaluated by MMSE scores. Results obtained from SR-BI-enriched Fu5AH and ABCA1-enriched J774 cells revealed that AD impaired the interaction of HDL and apoA-I with both the ABCA1 transporter and SR-BI receptor. Purified apoA-I from AD patients also failed to remove free excess cholesterol from ABCA1-enriched J774 macrophages. Interestingly, the decrease in plasma α-tocopherol content and the increase in MDA formation and HDL relative electrophoretic mobility indicated that AD patients had higher levels of oxidative stress. The anti-inflammatory activity of HDL was also significantly lower in AD patients as measured by the level of ICAM-1 expression. In conclusion, our study provides evidence for the first time that the functionality of HDL is impaired in AD and that this alteration might be caused by AD-associated oxidative stress and inflammation.
authors.affiliation: Research Centre on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada. a.khalil@USherbrooke.ca
authors.forename: Abdelouahed
authors.initials: A
authors.lastname: Khalil
authors.forename: Hicham
authors.initials: H
authors.lastname: Berrougui
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D016632:Apolipoprotein A-I / Q000097:blood; D002460:Cell Line; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress; D051122:Scavenger Receptors, Class B / Q000097:blood*; D024502:alpha-Tocopherol / Q000097:blood
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D024502:alpha-Tocopherol