Investigating the association between hepcidin and brain amyloid-β burden in cognitively normal elderly individuals

Introduction: Metal dyshomeostasis is one of the predominant pathways in the pathogenesis of Alzheimer's disease (AD). Hepcidin is a protein synthesised in the liver, and it is known to play a key role in iron regulation. Hepcidin level alteration has been previously observed in the brain and blood samples of patients with AD, however, it has not been investigated yet in preclinical AD, i.e. prior to cognitive impairment. Objective: Investigate the association of serum hepcidin with neocortical amyloid load (NAL). Also, investigate its association with AD risk factors, cognitive performance and other iron related proteins. Methods: Serum hepcidin concentration was measured by using the enzyme-linked immunosorbent assay in participants from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort. Participants were aged 65-90 years and they were cognitively normal based on the neuropsychological tests. Subjects were categorised into the high NAL (n=35) and low NAL (n=65) groups via positron emission tomography (PET) scans using a standard uptake value ratio cutoff = 1.35. Results: Serum hepcidin levels were significantly higher in participants with high NAL compared to those with low NAL. Moreover, a significant positive association was observed between the serum hepcidin and NAL. To evaluate the potential of hepcidin in distinguishing the low NAL and high NAL groups, receiver operating characteristic (ROC) curves were generated using the logistic regression. The area under the curve slightly increased from 0.78 in the 'base model' to 0.81 in the 'base+hepcidin' model. Conclusion: Current findings show that increased serum hepcidin is an early event in AD pathogenesis. Therefore, hepcidin can be considered as a potential biomarker within a diagnostic panel of markers for AD, and could be helpful in the process of identifying therapeutic targets for AD.