Evaluation of a Prototype Point-of-care Instrument Based on Monochromatic X-Ray Fluorescence Spectrometry: Potential for Monitoring Trace Element Status of Subjects with Neurodegenerative Disease

Abstract

Assessment of trace elements such as Cu, Zn, and Se in patients with neurodegenerative disease, such as Alzheimer's (AD) and Parkinson's disease (PD), may be useful in etiologic studies and in assessing the risk of developing these conditions. A prototype point-of-care (POC) instrument based on monochromatic x-ray fluorescence (M-XRF) was assembled and evaluated for the determination of Cu, Zn, and Se in whole blood, plasma, and urine. The prototype instrument was validated using certified reference materials for Cu and Zn in serum/plasma, and the reported bias and relative imprecision were <10%. The M-XRF prototype performance was further assessed using human specimens collected from AD and PD subjects, and was found to be satisfactory (<20% bias) for monitoring Cu and Zn levels in plasma and whole blood. However, the prototype M-XRF sensitivity was not sufficient for quantifying Cu, Zn, or Se in urine. Nonetheless, while validating the prototype instrument, body fluids (whole blood, plasma, and urine) were collected from 19 AD patients, 23 PD patients, and 24 controls specifically for trace element analysis using well-validated methods based on inductively coupled plasma mass spectrometry (ICP-MS). This limited biomonitoring study provided robust data for up to 16 elements including Sb, As, Ba, Cd, Cs, Co, Cr, Cu, Hg, Pb, Mo, Se, Tl, Sn, Zn, and U in plasma, whole blood, and urine. The results did not indicate any significant differences in most trace elements studied between AD or PD patients compared to controls, although the sample size is limited. A statistically significant increase in plasma Se was identified for PD patients relative to AD patients, but this could be due to age differences.

Reactive Oxygen Species and Selenium in Epilepsy and in Other Neurological Disorders

“…Low plasma selenium concentrations are associated with subtle neurological impairments reflected in soft neurological signs [84,85]. Plasma Se was the only statistically significant difference of up to 16 elements identified for PD patients [86] relative to Alzheimer's disease patients. Redox-active role is evidenced by an increased lipid peroxidation and reduced glutathione levels [87] and high concentration of iron and free radical generation via autocatalytic mechanisms within neuromelanincontaining catecholaminergic neurons in the substantia nigra.…”

Copper Imbalance in Alzheimer’s Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study Evaluating ATP7B Gene Variants

“…Sixty-nine full-text articles were assessed for eligibility. We excluded from the original 69 one study that did not report SD [38], one that reported a geometrical mean [39], and two that did not report the absolute value of Cu levels [10,40]. We also excluded the study by Alimonti et al [41] because the data partially overlapped with some shown in a paper by Bocca and colleagues [42].…”

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

“…149,150 Conventional optical uorescence, however, exhibits several limitations as a POC diagnostic strategy due to the lack of portability, high cost, requirement of a specic prociency from the expert, and unsuitability in ambulatory environment. 150 To addresses these issues, a great effort has been made to develop a compact, portable, multiplexed, and cost-effective uorescent modalities [151][152][153][154][155][156] such as smartphone embedment, 157 uorescent lateral ow assay 158 etc.…”