Biometals as Potential Predictors of the Neurodegenerative Decline in Alzheimer's Disease.

Liseth K Lavado,Michelle Zhang,Urvish K Patel,Sohim Khan,Karan Patel

doi:10.7759/cureus.5573

Abstract

Alzheimer’s Disease (AD) is a debilitating neurodegenerative disease that is diagnosed by gradual memory loss and certain cognitive impairments involving attention, reasoning, and language. Most of the research on Alzheimer’s disease focuses on the correlation of its neuropathological changes in the neurofibrillary tangles caused by hyper-phosphorylated tau protein and β-amyloid plaques with respect to cognitive impairment. Its pathology, however, remains incompletely understood. Currently, research has demonstrated that environmental factors such as biometals play a crucial role in exacerbating AD progression. The present review examines the role of metals in AD progression and how metal dyshomeostasis attributes to AD pathogenesis. It was found that certain metals possess both beneficial and harmful properties in terms of AD progression. Depending upon the concentration of the metal of interest, copper, zinc, iron, and selenium have general beneficial properties. However, when present in excess, they can lead to oxidative stress and hyperphosphorylation of tau protein, amongst other harmful effects, while calcium and magnesium were seen to have beneficial effects by regulating biometal uptake. In this review, we have provided evidential studies that focus on the involvement of certain metals in antioxidant pathways leading to the formation of reactive species indicative of neurodegeneration.

Highlights

BackgroundAlzheimer’s disease (AD) is an irreversible brain disorder that affects over 6 million individuals
The present review examines the role of metals in Alzheimer’s Disease (AD) progression and how metal dyshomeostasis attributes to AD pathogenesis
The inability of Presenilin to regulate copper and zinc uptake leads to an increase in the concentrations of these metals and contributes to metal dyshomeostasis, which further leads to the oxidative stress seen in AD patients [5]

Summary

Introduction

Alzheimer’s disease (AD) is an irreversible brain disorder that affects over 6 million individuals. Research funding for Alzheimer’s is higher than it has ever been, there is still no effective therapeutic agent to this disease. AD originates in the medial temporal lobe and follows the perforant path from the entorhinal cortex to the dentate gyrus, before moving to the frontal lobe toward the posterior cingulate cortex. It is a progressive disease and has an intermediate form known as Mild Cognitive Impairment (MCI) before it is clinically diagnosed as Alzheimer’s Disease [1]

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