ArticleBrain pathology (Zurich, Switzerland)2019
Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice.
Article in Brain pathology (Zurich, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 196 citations in OpenAlex.
- Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Iron dysregulation in the central nervous system: implications for autism spectrum disorder.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Multimodal MRI insights into hippocampal pathological changes across the Alzheimer's disease continuum: advances and challenges.Japanese journal of radiology · 2026Review
- An ApoE-Associated Low-Inflammatory Microglial State Emerges After Inflammatory Challenge in Alzheimer's Disease Mice.Neuroscience bulletin · 2026Article
- Deep Plasma Proteomics-Based Diagnostic Panel for Early Detection of Amnestic Mild Cognitive Impairment.Journal of proteome research · 2026Article
- Iron accumulation in the corpus callosum: a quantitative MRI study in relapsing-remitting multiple sclerosis.Irish journal of medical science · 2026Article
- Microglia in Alzheimer's Disease: From Homeostatic Guardians to Multifaceted Drivers of Neuropathology.Cells · 2026Review
- Cortical Iron and Mesostriatal Dopamine Function in Schizophrenia: A Positron Emission Tomography and Magnetic Resonance Imaging Study.Schizophrenia bulletin · 2026Article
- miR‑223‑3p promotes microglial lactylation and M1 polarization via the FBXW7/Notch1/Hes1/SIRT1 axis.International journal of molecular medicine · 2026Article
- Reimagining the contribution of iron in Parkinson's disease.Neurobiology of disease · 2026Review
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Article
- Role and mechanisms of ferroptosis in cognitive impairment: From molecular pathways to therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Review
- Glial lactate metabolism and transport in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Neuroinflammation in Alzheimer's disease: glial crosstalk, pathological modulation, and therapeutic implications.Frontiers in immunology · 2026Review
- 27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine.npj aging · 2025Article
- Quantitative susceptibility mapping at 7T as a biomarker of post- and interictal extravascular iron in patients with focal epilepsy.EBioMedicine · 2025Article
- Review
65 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the changes that typify Alzheimer's disease (AD) are neuroinflammation and microglial activation, amyloid deposition perhaps resulting from compromised microglial function and iron accumulation. Data from Genome Wide Association Studies (GWAS) identified a number of gene variants that endow a significant risk of developing AD and several of these encode proteins expressed in microglia and proteins that are implicated in the immune response. This suggests that neuroinflammation and the accompanying microglial activation are likely to contribute to the pathogenesis of the disease. The trigger(s) leading to these changes remain to be identified. In this study, we set out to examine the link between the inflammatory, metabolic and iron-retentive signature of microglia in vitro and in transgenic mice that overexpress the amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1 mice), a commonly used animal model of AD. Stimulation of cultured microglia with interferon (IFN)γ and amyloid-β (Aβ) induced an inflammatory phenotype and switched the metabolic profile and iron handling of microglia so that the cells became glycolytic and iron retentive, and the phagocytic and chemotactic function of the cells was reduced. Analysis of APP/PS1 mice by magnetic resonance imaging (MRI) revealed genotype-related hypointense areas in the hippocampus consistent with iron deposition, and immunohistochemical analysis indicated that the iron accumulated in microglia, particularly in microglia that decorated Aβ deposits. Isolated microglia prepared from APP/PS1 mice were characterized by a switch to a glycolytic and iron-retentive phenotype and phagocytosis of Aβ was reduced in these cells. This evidence suggests that the switch to glycolysis in microglia may kick-start a cascade of events that ultimately leads to microglial dysfunction and Aβ accumulation.
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