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. 2016 Apr;150(2):292-300.
doi: 10.1093/toxsci/kfv325. Epub 2015 Dec 31.

Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls

Steven T Szabo  1 , G Jean Harry  2 , Kathleen M Hayden  3 , David T Szabo  4 , Linda Birnbaum  5
Affiliations

Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls

Steven T Szabo et al. Toxicol Sci. 2016 Apr.

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.

Keywords: amyloid beta; brain; cerebral spinal fluid; heavy metals; neurodegenerative disease.

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Figures

FIG. 1.
FIG. 1.
Levels of metals (ng/g tissue weight) in the frontal cortex (FC) of normal elderly control subjects and Alzheimer’s disease cases at age of death. All samples reported exceeded the level of quantitation.
See this image and copyright information in PMC

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