ArticleJournal of Alzheimer's disease : JAD2021
Upregulation of Local Hepcidin Contributes to Iron Accumulation in Alzheimer's Disease Brains.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 18 citations in OpenAlex.
- Associations of Iron Indicators with Cognitive Impairment Risk in Postmenopausal Women: Evidence from a Matched Case-Control Study and Back Propagation Neural Network Model.Molecular neurobiology · 2026Article
- Ferritin in ferroptosis: Implications for neurodegenerative diseases (Review).International journal of molecular medicine · 2026Review
- Reexamining the Role of Amyloid β Clearance from the Brain: Exporting Labile Iron from the Interstitial Fluid Performs a Protective Function.International journal of molecular sciences · 2026Review
- Metabolic Regulatory Networks in Ferroptosis During Alzheimer's Disease, Mechanisms of Glial Cell Action, and Pathological Correlations with Neuritic Plaques.International journal of general medicine · 2026Review
- Anemia, iron deficiency, and blood biomarkers for Alzheimer disease: clinical interpretation and dementia risk stratification.Frontiers in nutrition · 2026Review
- The role of ferroptosis in Alzheimer's disease: Mechanisms and therapeutic potential (Review).Molecular medicine reports · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Nasal exudate for diagnosis of stroke: fundamental studies through iron fractionation, total iron, and targeted protein determinations.Analytical and bioanalytical chemistry · 2024Article
- Lipocalin-2 Secreted by the Liver Regulates Neuronal Cell Function Through AKT-Dependent Signaling in Hepatic Encephalopathy Mouse Model.Clinical nutrition research · 2023Article
- Cerebral Iron Deposition in Neurodegeneration.Biomolecules · 2022Review
- Aging is associated with increased brain iron through cortex-derived hepcidin expression.eLife · 2022Article
- Iron Dyshomeostasis and Ferroptosis: A New Alzheimer's Disease Hypothesis?Frontiers in aging neuroscience · 2022Review
- The Role of Microglia in Alzheimer's Disease From the Perspective of Immune Inflammation and Iron Metabolism.Frontiers in aging neuroscience · 2022Review
- Iron overload and neurodegenerative diseases: What can we learn fromToxicology research and applicationArticle
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAccumulation of iron is a consistent feature of Alzheimer's disease (AD) brains. The underlying cause, however, remains debatable.
objectiveTo explore whether local hepcidin synthesized by brain cells contributes to iron accumulation in AD brains.
methodsBrain tissue from the cingulate cortex of 33 cases of AD pre-assigned to Braak stage I-VI, 6 cases of non-dementia, and 15 cases of non-AD dementia were analyzed for transcriptional upregulation of hepcidin by RT-qPCR and RT-PCR. Change in the expression of ferritin, ferroportin (Fpn), microglial activation marker Iba1, IL-6, and TGFβ2 was determined by western blotting. Total tissue iron was determined by colorimetry.
resultsSignificant transcriptional upregulation of hepcidin was observed in Braak stage III-VI relative to Braak stage I and II, non-AD dementia, and non-dementia samples. Ferritin was increased in Braak stage V, and a significant increase in tissue iron was evident in Braak stage III-VI. The expression of Iba1 and IL-6 was also increased in Braak stage III-VI relative to Braak stage I and II and non-AD dementia samples. Amyloid-β plaques were absent in most Braak stage I and II samples, and present in Braak stage III-VI samples with few exceptions.
conclusionThese observations suggest that upregulation of brain hepcidin is mediated by IL-6, a known transcriptional activator of hepcidin. The consequent downregulation of Fpn on neuronal and other cells results in accumulation of iron in AD brains. The increase in hepcidin is disease-specific, and increases with disease progression, implicating AD-specific pathology in the accumulation of iron.
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