ArticleNature aging2021
Hypoxia compromises the mitochondrial metabolism of Alzheimer's disease microglia via HIF1.
Article in Nature aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Pooled it
- Microglia-targetedMaterials today. Bio · 2026Article
- 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
- Reduced microvascular coverage links a hypoxia-associated niche to microglial autophagic dysfunction in Parkinson's disease.Acta neuropathologica communications · 2026Article
- An ApoE-Associated Low-Inflammatory Microglial State Emerges After Inflammatory Challenge in Alzheimer's Disease Mice.Neuroscience bulletin · 2026Article
- Review
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Comprehensive single-cell transcriptomic atlas of microglia in Alzheimer's disease mouse models.Molecular psychiatry · 2026Article
- Human IL-34 Deficiency Primes Microglia Toward Alzheimer's Disease-Associated States.medRxiv : the preprint server for health sciences · 2026Article
- Transcriptional analyses identify pericyte-centered signaling programs altered by sex and brain region in Alzheimer's Disease.Communications biology · 2026Article
- Microglial Activation Under Hypoxic Conditions in Early Alzheimer's Disease: Can Natural SIRT1 Activators Be Therapeutic Allies in the Inflammation-Energy Axis?Phytotherapy research : PTR · 2026Review
- Multiscale Approximations to Understand the Complex Role of Microglia in Alzheimer's Disease.The European journal of neuroscience · 2026Review
- Hypoxia-induced autophagic degradation of HIF-1α attenuates cellular aging and extends mammalian lifespan.Nature aging · 2026Article
- Dysfunction of the neurovascular unit as a temporal driver in Alzheimer's pathogenesis.Translational neurodegeneration · 2026Review
- Beyond the neuron: Exosomes as intercellular modulators of mitochondrial networks in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A HIF1A variant impacts long-term disability and smoldering inflammation in multiple sclerosis.Acta neuropathologica · 2026Article
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- Dynamic changes in mitochondria support phenotypic flexibility of microglia.Nature communications · 2025Article
- C9orf72 hexanucleotide repeat expansions impair microglial response in ALS.Nature neuroscience · 2025Article
- 2-Oxoglutarate Analog-Based Biomolecular Tools for Exploring Structure-Activity Relationships in Nonheme Iron Enzymes.Chembiochem : a European journal of chemical biology · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic Alzheimer's disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.