Examining Novel Treatment Approaches and Problems in Alzheimer's: An Overview

Abstract

Discovered in 1907, Alzheimer’s Disease (AD) encompasses various etiologies, yet its precise cause remains elusive, and a definitive curative treatment has eluded researchers for over a century. AD presents itself in two main forms: (1) the genetic variant, autosomal dominant AD (ADAD), constituting less than 1% of cases and typically appearing before the age of 65, and (2) the sporadic form, referred to as Sporadic Alzheimer’s Disease (SAD), generally emerging after the age of 65, with the risk doubling every five years. This review specifically focuses on Sporadic SAD, underscoring its strong connection to the aggregation of the normal protein β-amyloid (Aβ) within the neocortex. Recent findings suggest that the precipitation and toxicity of Aβ in AD result from abnormal interactions with neocortical metal ions, notably Zn, Cu, and Fe. Despite this, Aβ might also play a role in maintaining normal metal ion homeostasis. The rise in brain Cu and Fe levels with age has the potential to hypermetalate the Aβ peptide, initiating the catalytic production of hydrogen peroxide (H2O2), ultimately resulting in Aβ toxicity and auto-oxidation. The increased prevalence of AD in females is hypothesized to be associated with the elevated constitutive activity of the synaptic Zn transporter, ZnT3. This comprehensive review delves into the latest treatment methodologies and strategies targeting modifiable risk factors for AD, offering insights into the ongoing quest to address and mitigate the complexities of this neurodegenerative disease.