A Pilot of the Feasibility of Using the Iron-Chelator Deferiprone on Mild Cognitive Impairment

Iron chelation's mechanism of action (MOA) in Alzheimer's disease (AD) is uncertain. Potential MOA include reversal of aluminum (AL) toxicity, the prevention of a-beta aggregation, β-amyloid disaggregation, and the obstruction of microbacterial and viral parasitism. The latter mechanism involves augmentation of innate immunity, and disruption of microbacterial iron metabolism. Infectious models of AD's pathophysiology have been recently proposed. Iron blocks toll-like receptor (TLR) initiated anti-microbial actions mediated via gamma-interferon (IFN-γ) tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10). These biomarkers are of interest because they have also been associated with our novel latent dementia phenotype (i.e., "d" for "dementia") in the Texas Alzheimer's Research and Care Consortium (TARCC). "d" is a continuous measure of dementia severity that can be constructed from any cognitive battery that also includes a measure of Instrumental Activities of Daily Living (IADL). Serum biomarkers might "trigger" dementing processes without participating in their later stages. Thus, the investigators have indications as to who might benefit from iron-chelation and when the intervention might be best applied. This knowledge may help them detect an effect of deferiprone on prospective change in "d" and even on MCI conversion in TARCC NHW (Non Hispanic White) subjects.