Abstract
Metal/mineral dyshomeostasis has been implicated in the development of Alzheimer’s disease (AD). The aim of the study was to investigate the difference in absolute and percentage levels of plasma phosphorus, calcium, iron, zinc, copper, selenium in cognitively normal (CN) and AD subjects. Total reflection X-ray fluorescence (TXRF) spectroscopy was used to detect plasma metals/minerals in CN and AD subjects (n = 44 per group). TXRF detected significantly increased plasma levels of phosphorus (p = 1.33 × 10−12) and calcium (p = 0.025) in AD compared to CN subjects, with higher phosphorus/calcium (p = 2.55 × 10−14) ratio in the former. Percentage concentrations calculated for phosphorus, calcium, iron, zinc, copper, selenium by dividing the concentration of each element by the total concentration of these elements and multiplying by 100%, demonstrated phosphorus was higher in AD compared to CN subjects, while calcium, iron, zinc, copper and selenium were lower in AD subjects, with area under the curves as high as 0.937 (p = 6 × 10−5) computed from receiver operating curves. With exclusion of high levels of phosphorus and calcium from percentage calculations, iron levels remained low in AD whereas zinc was higher in AD, and copper and selenium levels were similar. We demonstrate altered distribution of elements in the plasma of AD subjects with high interdependencies between elemental levels and propose the potential of TXRF measurements for disease monitoring.
Highlights
Metal/mineral dyshomeostasis has been implicated in the development of Alzheimer’s disease (AD)
Percentage concentrations calculated for phosphorus, calcium, iron, zinc, copper, selenium by dividing the concentration of each element by the total concentration of these elements and multiplying by 100%, demonstrated phosphorus was higher in AD compared to cognitively normal (CN) subjects, while calcium, iron, zinc, copper and selenium were lower in AD subjects, with area under the curves as high as 0.937 (p = 6 × 10−5) computed from receiver operating curves
We report a pattern of increased percentage of phosphorus but decreased calcium, iron, copper, zinc and selenium in the plasma from AD subjects compared to CN
Summary
Metal/mineral dyshomeostasis has been implicated in the development of Alzheimer’s disease (AD). The aim of the study was to investigate the difference in absolute and percentage levels of plasma phosphorus, calcium, iron, zinc, copper, selenium in cognitively normal (CN) and AD subjects. Alzheimer’s disease (AD) is the most common cause of dementia in the elderly population with a predicted incidence of 115.4 million cases by 2050 It is characterised by pathological inclusions of extracellular ß-amyloid (Aß) plaques and intracellular neurofibrillary tangles[1]. Metal dyshomeostasis ( iron, zinc and copper) has recently been implicated in the development of AD2 These metals can accentuate plaque formation and affect tau hyperphosphorylation albeit to a lesser extent. Investigators have tested whether alterations of brain metals and other elements are peripherally reflected to potentially aid in diagnosis and disease monitoring[5,6,8]. A few studies do report analysis of a panel of metals by inductively-coupled plasma mass spectroscopy (ICP-MS) showing differences between cognitively normal (CN), mild cognitive impairment (MCI) and AD2,3
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