Iron Chelators and Alzheimer’s Disease Clinical Trials

Article type: Research Article

Authors: Mandal, Pravat K.^{a; b; c; *} | Maroon, Joseph C.^b | Samkaria, Avantika^{a; d} | Arora, Yashika^a | Sharma, Shallu^{a; e} | Pandey, Ashutosh^{a; f}

Affiliations: [a] Neuroimaging and Neurospectroscopy (NINS) Laboratory, National Brain Research Centre, Gurgaon, India | [b] Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA | [c] Florey Institute of Neuroscience and Mental Health, Melbourne School of Medicine Campus, Melbourne, VIC, Australia | [d] Department of Forensic Science, Chandigarh University, Mohali, Punjab, India | [e] School of Computer Science Engineering and Technology, Bennett University, Greater Noida, UP, India | [f] Department of Medicine, NEIGRIHMS, Shillong, Meghalaya, India

Correspondence: [*] Correspondence to: Dr. Pravat Kumar Mandal, Professor and Scientist VII, Neuroimaging and Neurospectroscopy (NINS), Laboratory National Brain Research Centre, India. E-mail: pravat.mandal@gmail.com; Adjunct Professor, Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. E-mail: mandalpk@upmc.edu; Honorary Professor, Florey Institute of Neuroscience and Mental Health, Melbourne School of Medicine Campus, Melbourne, Australia. E-mail: pravat.mandal@florey.edu.au.

Abstract: Alzheimer’s disease (AD) is a major neurodegenerative disorder impacting millions of people with cognitive impairment and affecting activities of daily living. The deposition of neurofibrillary tangles of hyperphosphorylated tau proteins and accumulation of amyloid-β (Aβ) are the main pathological characteristics of AD. However, the actual causal process of AD is not yet identified. Oxidative stress occurs prior to amyloid Aβ plaque formation and tau phosphorylation in AD. The role of master antioxidant, glutathione, and metal ions (e.g., iron) in AD are the frontline area of AD research. Iron overload in specific brain regions in AD is associated with the rate of cognitive decline. We have presented the outcome from various interventional trials involving iron chelators intended to minimize the iron overload in AD. To date, however, no significant positive outcomes have been reported using iron chelators in AD and warrant further research.

Keywords: Alzheimer’s disease, clinical trials, iron-chelator, iron overload, oxidative stress, prooxidant

DOI: 10.3233/JAD-240605

Journal: Journal of Alzheimer's Disease, vol. 100, no. s1, pp. S243-S249, 2024