Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by cognitive decline and neuropathological hallmarks, including β-amyloid (Aβ) plaques, Tau tangles, synaptic dysfunction and neurodegeneration. Emerging evidence suggests that abnormal iron (Fe) metabolism plays a role...
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MDPI AG
2024-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/3/295 |
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| author | Susana Junceda María Cruz-Alonso Beatriz Fernandez Rosario Pereiro Eva Martínez-Pinilla Ana Navarro |
| author_facet | Susana Junceda María Cruz-Alonso Beatriz Fernandez Rosario Pereiro Eva Martínez-Pinilla Ana Navarro |
| author_sort | Susana Junceda |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by cognitive decline and neuropathological hallmarks, including β-amyloid (Aβ) plaques, Tau tangles, synaptic dysfunction and neurodegeneration. Emerging evidence suggests that abnormal iron (Fe) metabolism plays a role in AD pathogenesis, but the precise spatial distribution of the Fe and its transporters, such as ferroportin (FPN), within affected brain regions remains poorly understood. This study investigates the distribution of Fe and FPN in the CA1 region of the human hippocampus in AD patients with a micrometer lateral resolution using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). For this purpose, we visualized and quantified Fe and FPN in three separated CA1 layers: stratum molecular–radial (SMR), stratum pyramidal (SP) and stratum oriens (SO). Additionally, chromogenic immunohistochemistry was used to examine the distribution and colocalization with Tau and Aβ proteins. The results show that Fe accumulation was significantly higher in AD brains, particularly in SMR and SO. However, FPN did not present significantly changes in AD, although it showed a non-uniform distribution across CA1 layers, with elevated levels in SP and SO. Interestingly, minimal overlap was observed between Fe and FPN signals, and none between Fe and areas rich in neurofibrillary tangles (NFTs) or neuritic plaques (NP). In conclusion, the lack of correlation between Fe and FPN signals suggests complex regulatory mechanisms in AD Fe metabolism and deposition. These findings highlight the complexity of Fe dysregulation in AD and its potential role in disease progression. |
| first_indexed | 2024-04-24T18:30:44Z |
| format | Article |
| id | doaj.art-ef4eb2c79adc4b6abcfd09ed7193a2d6 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-24T18:30:44Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ef4eb2c79adc4b6abcfd09ed7193a2d62024-03-27T13:27:53ZengMDPI AGBiomolecules2218-273X2024-03-0114329510.3390/biom14030295Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human HippocampusSusana Junceda0María Cruz-Alonso1Beatriz Fernandez2Rosario Pereiro3Eva Martínez-Pinilla4Ana Navarro5Servicio de Anatomo-Patología, Hospital Universitario Central de Asturias–HUCA, Av Roma s/n, 33011 Oviedo, SpainDepartment of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Julian Claveria 8, 33006 Oviedo, SpainDepartment of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Julian Claveria 8, 33006 Oviedo, SpainDepartment of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Julian Claveria 8, 33006 Oviedo, SpainInstituto de Neurociencias del Principado de Asturias (INEUROPA), 33006 Oviedo, SpainInstituto de Neurociencias del Principado de Asturias (INEUROPA), 33006 Oviedo, SpainAlzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by cognitive decline and neuropathological hallmarks, including β-amyloid (Aβ) plaques, Tau tangles, synaptic dysfunction and neurodegeneration. Emerging evidence suggests that abnormal iron (Fe) metabolism plays a role in AD pathogenesis, but the precise spatial distribution of the Fe and its transporters, such as ferroportin (FPN), within affected brain regions remains poorly understood. This study investigates the distribution of Fe and FPN in the CA1 region of the human hippocampus in AD patients with a micrometer lateral resolution using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). For this purpose, we visualized and quantified Fe and FPN in three separated CA1 layers: stratum molecular–radial (SMR), stratum pyramidal (SP) and stratum oriens (SO). Additionally, chromogenic immunohistochemistry was used to examine the distribution and colocalization with Tau and Aβ proteins. The results show that Fe accumulation was significantly higher in AD brains, particularly in SMR and SO. However, FPN did not present significantly changes in AD, although it showed a non-uniform distribution across CA1 layers, with elevated levels in SP and SO. Interestingly, minimal overlap was observed between Fe and FPN signals, and none between Fe and areas rich in neurofibrillary tangles (NFTs) or neuritic plaques (NP). In conclusion, the lack of correlation between Fe and FPN signals suggests complex regulatory mechanisms in AD Fe metabolism and deposition. These findings highlight the complexity of Fe dysregulation in AD and its potential role in disease progression.https://www.mdpi.com/2218-273X/14/3/295Alzheimer’s diseaseiron transport proteinsferroportiniron homeostasisβ-amyloidTau |
| spellingShingle | Susana Junceda María Cruz-Alonso Beatriz Fernandez Rosario Pereiro Eva Martínez-Pinilla Ana Navarro Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus Biomolecules Alzheimer’s disease iron transport proteins ferroportin iron homeostasis β-amyloid Tau |
| title | Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus |
| title_full | Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus |
| title_fullStr | Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus |
| title_full_unstemmed | Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus |
| title_short | Iron Dysregulation in Alzheimer’s Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus |
| title_sort | iron dysregulation in alzheimer s disease la icp ms bioimaging of the distribution of iron and ferroportin in the ca1 region of the human hippocampus |
| topic | Alzheimer’s disease iron transport proteins ferroportin iron homeostasis β-amyloid Tau |
| url | https://www.mdpi.com/2218-273X/14/3/295 |
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