Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration
The involvement of iron in the pathogenesis of Alzheimer’s disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/3/511 |
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| author | Steven M. LeVine Sheila Tsau Sumedha Gunewardena |
| author_facet | Steven M. LeVine Sheila Tsau Sumedha Gunewardena |
| author_sort | Steven M. LeVine |
| collection | DOAJ |
| description | The involvement of iron in the pathogenesis of Alzheimer’s disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from baseline and modified iron histochemical protocols, iron was found to be more tightly bound within cortical sections from patients with high levels of AD pathology compared to subjects with a diagnosis of something other than AD. To begin examining whether the bound iron could cause a functional iron deficiency, a protein-coding gene expression dataset of initial, middle, and advanced stages of AD from olfactory bulb tissue was analyzed for iron-related processes with an emphasis on anemia-related changes in initial AD to capture early pathogenic events. Indeed, anemia-related processes had statistically significant alterations, and the significance of these changes exceeded those for AD-related processes. Other changes in patients with initial AD included the expressions of transcripts with iron-responsive elements and for genes encoding proteins for iron transport and mitochondrial-related processes. In the latter category, there was a decreased expression for the gene encoding pitrilysin metallopeptidase 1 (PITRM1). Other studies have shown that PITRM1 has an altered activity in patients with AD and is associated with pathological changes in this disease. Analysis of a gene expression dataset from PITRM1-deficient or sufficient organoids also revealed statistically significant changes in anemia-like processes. These findings, together with supporting evidence from the literature, raise the possibility that a pathogenic mechanism of AD could be a functional deficiency of iron contributing to neurodegeneration. |
| first_indexed | 2024-03-11T06:51:06Z |
| format | Article |
| id | doaj.art-edcaafbe92e3431c83f9d69ce487d8bd |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T06:51:06Z |
| publishDate | 2023-03-01 |
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| series | Brain Sciences |
| spelling | doaj.art-edcaafbe92e3431c83f9d69ce487d8bd2023-11-17T10:00:54ZengMDPI AGBrain Sciences2076-34252023-03-0113351110.3390/brainsci13030511Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances NeurodegenerationSteven M. LeVine0Sheila Tsau1Sumedha Gunewardena2Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USAThe involvement of iron in the pathogenesis of Alzheimer’s disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from baseline and modified iron histochemical protocols, iron was found to be more tightly bound within cortical sections from patients with high levels of AD pathology compared to subjects with a diagnosis of something other than AD. To begin examining whether the bound iron could cause a functional iron deficiency, a protein-coding gene expression dataset of initial, middle, and advanced stages of AD from olfactory bulb tissue was analyzed for iron-related processes with an emphasis on anemia-related changes in initial AD to capture early pathogenic events. Indeed, anemia-related processes had statistically significant alterations, and the significance of these changes exceeded those for AD-related processes. Other changes in patients with initial AD included the expressions of transcripts with iron-responsive elements and for genes encoding proteins for iron transport and mitochondrial-related processes. In the latter category, there was a decreased expression for the gene encoding pitrilysin metallopeptidase 1 (PITRM1). Other studies have shown that PITRM1 has an altered activity in patients with AD and is associated with pathological changes in this disease. Analysis of a gene expression dataset from PITRM1-deficient or sufficient organoids also revealed statistically significant changes in anemia-like processes. These findings, together with supporting evidence from the literature, raise the possibility that a pathogenic mechanism of AD could be a functional deficiency of iron contributing to neurodegeneration.https://www.mdpi.com/2076-3425/13/3/511Alzheimer’s diseaseanemiahemehistochemistryironmitochondria |
| spellingShingle | Steven M. LeVine Sheila Tsau Sumedha Gunewardena Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration Brain Sciences Alzheimer’s disease anemia heme histochemistry iron mitochondria |
| title | Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration |
| title_full | Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration |
| title_fullStr | Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration |
| title_full_unstemmed | Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration |
| title_short | Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration |
| title_sort | exploring whether iron sequestration within the cns of patients with alzheimer s disease causes a functional iron deficiency that advances neurodegeneration |
| topic | Alzheimer’s disease anemia heme histochemistry iron mitochondria |
| url | https://www.mdpi.com/2076-3425/13/3/511 |
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