Metal and complementary molecular bioimaging in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, affecting over 27 million people worldwide. AD represents a complex neurological disorder which is best understood as the consequence of a number of interconnected genetic and lifestyle variables, which culminate in multiple changes to brain structure and function. These can be observed on a gross anatomical level in brain atrophy, microscopically in extracellular amyloid plaque and neurofibrillary tangle formation, and at a functional level as alterations of metabolic activity. At a molecular level, metal dyshomeostasis is frequently observed in AD due to anomalous binding of metals such as Iron (Fe), Copper (Cu), and Zinc (Zn), or impaired regulation of redox-active metals which can induce the formation of cytotoxic reactive oxygen species and neuronal damage. Metal chelators have been administered therapeutically in transgenic mice models for AD and in clinical human AD studies, with positive outcomes. As a result, neuroimaging of metals in a variety of intact brain cells and tissues is emerging as an important tool for increasing our understanding of the role of metal dysregulation in AD. Several imaging techniques have been used to study the cerebral metallo-architecture in biological specimens to obtain spatially resolved data on chemical elements present in a sample. Hyperspectral techniques, such as particle-induced X-ray emission (PIXE), energy dispersive X-ray spectroscopy (EDS), X-ray fluorescence microscopy (XFM), synchrotron X-ray fluorescence (SXRF), secondary ion mass spectrometry (SIMS), and laser ablation inductively coupled mass spectrometry (LA-ICPMS) can reveal relative intensities and even semi-quantitative concentrations of a large set of elements with differing spatial resolution and detection sensitivities. Other mass spectrometric and spectroscopy imaging techniques such as laser ablation electrospray ionization mass spectrometry (LA ESI-MS), MALDI imaging mass spectrometry (MALDI-IMS), and Fourier transform infrared spectroscopy (FTIR) can be used to correlate changes in elemental distribution with the underlying pathology in AD brain specimens. Taken together, these techniques provide new techniques to probe the pathobiology of AD and pave the way for identifying new therapeutic targets. The current review aims to discuss the advantages and challenges of using these emerging elemental and molecular imaging techniques, and highlight clinical achievements in AD research using bioimaging techniques.

Changes of erythrocyte element status of colectomysed cancerous patients: Retrospective study

“…On the other hand, it is well known, that elevated element concentrations, for instance Al; Fe; Cu; Zn level can cause disturbances in the redox homeostasis of healthy tissues, for example in neurons as it has been proven in many studies about Alzheimer's, Parkinson's or Wilson's disease, Friedrich ataxia and prion-diseases (Ward 2014, Butterfield 2014Singh 2010, Dusek 2014Braidy 2014). Since the chemotherapy associated cognitive impairment is not clearly understood yet, but oxidative stress has been confirmed in these cases, researches about associations with the element contents are necessary (Hurria 2007;Butterfield 2014).…”

Health Effects of Metals in Particulate Matter

“…At a molecular level metal dishomeostasis and mitochondria dysfunction in AD and PD and the cytoplasmic predominance of neuronal 8-hydroxy-Guanine supports mitochondria as the major source of ROS responsible for RNA oxidation and might induce DNA oxidation neuronal damage [84,85].…”

Carbon Monoxide and Iron Modulate Plasmatic Coagulation in Alzheimer’s disease

“…Alzheimer's disease (AD) is a major source of morbidity and mortality for millions of people worldwide, and intense investigation has led to multiple etiological constructs contributing to AD [1][2][3][4][5][6][7][8][9][10][11][12]. In addition to the recently reviewed, original 'amyloid cascade hypothesis' [1], the development and progression of AD have been associated with viral infection [2], vascular damage from pulse pressure [3], regional deposition of metals, such as iron, resulting in oxidant injury [4][5][6][7][8], metabolic syndrome and morbid obesity [8][9][10], and long term exposure to spontaneous cerebral microemboli [11,12].…”

“…In addition to the recently reviewed, original 'amyloid cascade hypothesis' [1], the development and progression of AD have been associated with viral infection [2], vascular damage from pulse pressure [3], regional deposition of metals, such as iron, resulting in oxidant injury [4][5][6][7][8], metabolic syndrome and morbid obesity [8][9][10], and long term exposure to spontaneous cerebral microemboli [11,12]. Of these various paradigms, the notion that spontaneous emboli, most likely due to systemic hypercoagulability, is of particular interest.…”