Pattern of Altered Plasma Elemental Phosphorus, Calcium, Zinc, and Iron in Alzheimer’s Disease

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.

Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology

“…Our finding of increased transferrin levels being associated with increased hippocampal volumes and improved MMSE scores underscores the importance of the role of transferrin to bind iron in a safe and redox-inactive form to distribute elsewhere. The relationship between plasma and brain iron needs to be established; one could hypothesize that the decreases in plasma iron [7,9] is due to increased partitioning of iron into the brain in AD [63]. Macrophages have been suggested to require the ferroxidase activity of ceruloplasmin to load iron onto transferrin.…”

“…Regional measures of hippocampal atrophy have been identified as strong predictors of progression to AD [4]. Emerging evidence suggests that brain and blood iron homeostasis is perturbed in AD, with studies showing decreased peripheral iron (anemia) and lower hemoglobin levels [5][6][7][8][9][10][11]. Anemia is a prevalent condition in the elderly and is associated with an increased risk of acquiring AD [7,8,12,13].…”

Spotlight on Ferroptosis: Iron-Dependent Cell Death in Alzheimer’s Disease

“…Ferritin works in concert with ferroportin, the only known cellular iron exporter, aided by the ferroxidase, ceruloplasmin, to regulate LIP (De Domenico et al, 2007). Tight regulation of iron metabolism is pivotal to ensure neuronal homeostasis-both iron excess and deficiency are associated with neurodegeneration (Goodman, 1953;Youdim, 2008;Ashraf et al, 2019).…”

Study of chromium, selenium and bromine concentrations in blood serum of patients with parenteral nutrition treatment using total reflection X-ray fluorescence analysis

“…Monitoring of blood serum elemental composition is important to the study the influence of environmental pollution, nutrition and/or occupational exposure on human health [10]. Another important aspect of such studies are element concentration changes in serum samples related to various diseases or treatment procedures [9,11]. The usefulness of the TXRF technique for measuring trace elements in serum samples has already been systematically tested and confirmed [12,13].…”