title: Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD).
abstract: Once biologically available aluminum bypasses gastrointestinal and blood-brain barriers, this environmentally-abundant neurotoxin has an exceedingly high affinity for the large pyramidal neurons of the human brain hippocampus. This same anatomical region of the brain is also targeted by the earliest evidence of Alzheimer's disease (AD) neuropathology. The mechanism for the selective targeting and transport of aluminum into the hippocampus of the human brain is not well understood. In an effort to improve our understanding of a pathological aluminum entry system into the brain, this study examined the aluminum content of 8 arteries that supply blood to the hippocampus, including the aorta and several cerebral arteries. In contrast to age-matched controls, in AD patients we found a gradient of increasing aluminum concentration from the aorta to the posterior cerebral artery that supplies blood to the hippocampus. Primary cultures of human brain endothelial cells were found to have an extremely high affinity for aluminum when compared to other types of brain cells. Together, these results suggest for the first time that endothelial cells that line the cerebral vasculature may have biochemical attributes conducive to binding and targeting aluminum to selective anatomical regions of the brain, such as the hippocampus, with potential downstream pro-inflammatory and pathogenic consequences.
authors.affiliation: Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Surjyadipta
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhao
authors.forename: James M
authors.initials: JM
authors.lastname: Hill
authors.forename: Frank
authors.initials: F
authors.lastname: Culicchia
authors.forename: Theodore P A
authors.initials: TP
authors.lastname: Kruck
authors.forename: Maire E
authors.initials: ME
authors.lastname: Percy
authors.forename: Aileen I
authors.initials: AI
authors.lastname: Pogue
authors.forename: J R
authors.initials: JR
authors.lastname: Walton
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Lukiw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000534:Alum Compounds / Q000633:toxicity*; D000535:Aluminum / Q000378:metabolism* / Q000633:toxicity; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D017136:Ion Transport; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D013054:Spectrophotometry, Atomic
chemical_list: D000534:Alum Compounds; C041524:aluminum sulfate; D000535:Aluminum
keywords: Aluminum sulfate; Alzheimer's disease; Endothelial cells; Genotoxicity; Human brain microvessel endothelial cells; Inflammation