title: Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls.
abstract: An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer's disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V), and zinc (Zn) using inductively coupled plasma sector field mass spectrometry. All metals, with exception of equivalent Pb levels, were lower in the VF, compared to FC. Within-subject comparisons demonstrated that VF levels were not representative of levels within brain tissue. The essential metals Cu, Fe, and Zn were found highest in both compartments. Cd, Hg, and V levels in the VF were below the limit of quantification. In AD cases, FC levels of Fe were higher and As and Cd were lower than levels in controls, while levels of As in the VF were higher. Parameter estimates for FC metal levels indicated an association of Braak stage and higher Fe levels and an association of Braak stage and lower As, Mn, and Zn levels. The data showed no evidence of an accumulation of nonessential metals within the AD brain and, with the exception of As, showed no significant shift in the ratio of FC to VF levels to indicate differential clearance.
authors.affiliation: *Veterans Affairs Medical Center, Mental Health Service Line, Durham, North Carolina 27705; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27705; steven.szabo@duke.edu.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Szabo
authors.affiliation: Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709;
authors.forename: G Jean
authors.initials: GJ
authors.lastname: Harry
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Joseph and Kathleen ADRC, Duke University Medical Center, Durham, North Carolina 27705;
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Hayden
authors.affiliation: RAI Services Company, Winston Salem, North Carolina 27102; and.
authors.forename: David T
authors.initials: DT
authors.lastname: Szabo
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Research Triangle Park, North Carolina 27709.
authors.forename: Linda
authors.initials: L
authors.lastname: Birnbaum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D019216:Metals, Heavy / Q000134:cerebrospinal fluid / Q000378:metabolism; D014131:Trace Elements / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D019216:Metals, Heavy; D014131:Trace Elements
keywords: amyloid beta; brain; cerebral spinal fluid; heavy metals; neurodegenerative disease