Getting the iron out: Phlebotomy for Alzheimer’s disease?

Abstract

SUMMARYThis communication explores the temporal link between the age-associated increase in body iron stores and the age-related incidence of Alzheimer's disease (AD), the most prevalent cause of senile dementia. Body iron stores that increase with age could be pivotal to AD pathogenesis and progression. Increased stored iron is associated with common medical conditions such as diabetes and vascular disease that increase risk for development of AD. Increased stored iron could also promote oxidative stress/free radical damage in vulnerable neurons, a critical early change in AD. A ferrocentric model of AD described here forms the basis of a rational, easily testable experimental therapeutic approach for AD, which if successful, would be both widely applicable and inexpensive. Clinical studies have shown that calibrated phlebotomy is an effective way to reduce stored iron safely and predictably without causing anemia. We hypothesize that reducing stored iron by calibrated phlebotomy to avoid iron deficiency will improve cerebrovascular function, slow neurodegenerative change, and improve cognitive and behavioral functions in AD. The hypothesis is eminently testable as iron reduction therapy is useful for chronic diseases associated with iron excess such as nonalcoholic steatohepatitis (NASH), atherosclerosis, hereditary hemochromatosis and thalassemia. Testing this hypothesis could provide valuable insight into the causation of AD and suggest novel preventive and treatment strategies.

Recent Achievements on Siderophore Production and Application

“…Several reports have already been published concerning the use of iron chelators to decrease the levels of free iron and consequentially to decrease the progression of neural degeneration [150,[154][155][156][157][158][159][160]. As an example of these treatments, the use of desferrioxamine (125 mg intramuscularly twice daily, 5 days per week for 24 months) slowed the rate of decline in patients with Alzheimer's disease.…”

“…As an example of these treatments, the use of desferrioxamine (125 mg intramuscularly twice daily, 5 days per week for 24 months) slowed the rate of decline in patients with Alzheimer's disease. Additionally, intravenous infusion of desferrioxamine (500 mg twice a week for 10 months) reduced serum ferritin, decreased brain iron and improved clinical status of a patient with aceruloplasminemia [159].…”

Prediction of Activity Spectra of Substances Assisted Prediction of Biological Activity Spectra of Potential Anti-Alzheimer’s Phytoconstituents

“…In AD, there is neuronal destruction and deterioration of neural connections in the cerebral cortex region of the brain along with a substantial loss of brain mass [2]. AD is invariably progressive and lethal within 5-10 years of its onset [3]. Death usually ensues due to complications of the chronic illness.…”

In vitro neurotoxic Fe(III) and Fe(III)-chelator activities in rat hippocampal cultures. From neurotoxicity to neuroprotection prospects

“…In line with the aforementioned, Fe(III) interactions with physiologically relevant ligands might render the metal ion and the ensuing biochemical processes toxic to brain neurons and/or glia [21]. One such substrate is quinic acid (QA), a low molecular mass α-hydroxycarboxylic acid metal ion chelator found in various plants and isolated from natural sources [22][23][24][25].…”