{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:00:04Z","timestamp":1780470004832,"version":"3.54.1"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebrovascular damage is increasingly recognized as an early event in the dementia continuum, occurring before typical Alzheimer\u2019s disease (AD) pathological changes. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor composed of HIF-1\u03b1 and HIF-1\u03b2 subunits which, under hypoxic conditions, dimerize and activate hypoxia response element (HRE)-containing genes. HIF-1\u03b1 has been reported to be implicated in neuroinflammation, a key feature of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study evaluated HIF1A and its negative regulator HIF1AN gene expression in peripheral blood mononuclear cells (PBMCs) from 308 cognitively healthy older individuals (controls) and 83 AD patients, and their associations with gene expression of HRE-containing inflammatory genes in PBMCs and corresponding protein concentrations in plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells from AD patients showed lower gene expression of both HIF1A and HIF1AN compared with controls, and this reduction was associated with higher odds of AD. In the overall cohort, after adjustment for age, sex, Apolipoprotein E \u03b54 status, and diagnosis, HIF1A gene expression was positively associated with interleukin (IL)-6, IL-10, tumor necrosis factor-\u03b1 (TNF-\u03b1), IL-1B, and triggering receptor expressed on myeloid cells-1 (TREM-1) gene expression, whereas HIF1AN gene expression was negatively associated with IL-6, IL-1B, and TREM-1 gene expression. Furthermore, HIF1A gene expression was positively associated with plasma IL-1\u03b2 and soluble TREM-1 concentrations, while HIF1AN gene expression was negatively associated with IL-10 concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, these findings support the use of peripheral cells to investigate HIF-1 pathway dysregulation in AD and suggest that altered HIF-1\u03b1 signaling may reflect impaired cellular responsiveness linked to neuroinflammatory processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1831919","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:00:17Z","timestamp":1780466417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the role of HIF-1 in peripheral blood mononuclear cells from older patients with Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Beatrice","family":"Arosio","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan","place":["Milan, Italy"]},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Ferri","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo Dionigi","family":"Rossi","sequence":"additional","affiliation":[{"name":"San Leopoldo Mandic Hospital","place":["Merate, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Aiello","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Caponetto","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche","place":["Ancona, Italy"]},{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fenoglio","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziano Angelo","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Montano","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan","place":["Milan, Italy"]},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"485","DOI":"10.3390\/cells13060485","article-title":"NF-\u03baB as an inducible regulator of inflammation in the central nervous system.","volume":"13","author":"Anilkumar","year":"2024","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"169203","DOI":"10.1155\/2014\/169203","article-title":"Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly.","volume":"2014","author":"Arosio","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"111872","DOI":"10.1016\/j.mad.2023.111872","article-title":"The influence of inflammation and frailty in the aging continuum.","volume":"215","author":"Arosio","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"112692","DOI":"10.1016\/j.exger.2025.112692","article-title":"The inflammatory profiling in a cohort of older patients suffering from cognitive decline and dementia.","volume":"201","author":"Arosio","year":"","journal-title":"Exp. Gerontol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1007\/s40520-025-03181-7","article-title":"Inflammaging and the sex-frailty paradox.","volume":"37","author":"Arosio","year":"","journal-title":"Aging Clin. Exp. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1293723","DOI":"10.3389\/fimmu.2024.1293723","article-title":"The factor inhibiting HIF regulates T cell differentiation and anti-tumour efficacy.","volume":"15","author":"Bargiela","year":"2024","journal-title":"Front. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.ccc.2010.12.006","article-title":"Triggering receptor expressed on myeloid cell 1.","volume":"27","author":"Barraud","year":"2011","journal-title":"Crit. Care Clin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s10020-025-01149-x","article-title":"Epitranscriptomic regulation of HIF-1: Bidirectional regulatory pathways.","volume":"31","author":"Benak","year":"2025","journal-title":"Mol. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6398","DOI":"10.1038\/s41467-024-50559-8","article-title":"Aging drives cerebrovascular network remodeling and functional changes in the mouse brain.","volume":"15","author":"Bennett","year":"2024","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1182\/blood-2010-06-292136","article-title":"Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: Identification of TREM-1 as a novel hypoxic marker in vitro and in vivo.","volume":"117","author":"Bosco","year":"2011","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1038\/35074114","article-title":"TREM-1 amplifies inflammation and is a crucial mediator of septic shock.","volume":"410","author":"Bouchon","year":"2001","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s41423-020-00591-7","article-title":"Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis.","volume":"18","author":"Boufenzer","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e69348","DOI":"10.7554\/eLife.69348","article-title":"Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis.","volume":"11","author":"Brereton","year":"2022","journal-title":"eLife"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e0197055","DOI":"10.1371\/journal.pone.0197055","article-title":"An investigation of cerebral oxygen utilization, blood flow and cognition in healthy aging.","volume":"13","author":"Catchlove","year":"2018","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3389\/fcell.2018.00132","article-title":"Reactive oxygen species formation in the brain at different oxygen levels: The role of hypoxia inducible factors.","volume":"6","author":"Chen","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nprot.2006.83","article-title":"The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on.","volume":"1","author":"Chomczynski","year":"2006","journal-title":"Nat. Protoc."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3699","DOI":"10.1172\/JCI84431","article-title":"HIF1\u03b1 and metabolic reprogramming in inflammation.","volume":"126","author":"Corcoran","year":"2016","journal-title":"J. Clin. Invest."},{"key":"B18","doi-asserted-by":"publisher","first-page":"858162","DOI":"10.3389\/fnagi.2022.858162","article-title":"VAMP2 expression and genotype are possible discriminators in different forms of dementia.","volume":"14","author":"Costa","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"18154","DOI":"10.1073\/pnas.0602235103","article-title":"Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity.","volume":"103","author":"Cummins","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B20","doi-asserted-by":"publisher","first-page":"216801","DOI":"10.1016\/j.canlet.2024.216801","article-title":"Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages.","volume":"590","author":"Dong","year":"2024","journal-title":"Cancer Lett."},{"key":"B21","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-1-0716-3754-8_9","article-title":"Analysis of human peripheral blood mononuclear cells in patients with neurodegenerative diseases.","volume":"2782","author":"Dover","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"6985","DOI":"10.1007\/s11033-014-3585-8","article-title":"Multiple correlations of mRNA expression and protein abundance in human cytokine profile.","volume":"41","author":"Du","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: The IWG-2 criteria.","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.mad.2019.01.005","article-title":"Apolipoprotein E gene in physiological and pathological aging.","volume":"178","author":"Ferri","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.tem.2016.09.005","article-title":"Inflammaging and \u201cGarb-aging.\u201d.","volume":"28","author":"Franceschi","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"B26","doi-asserted-by":"publisher","first-page":"E2705","DOI":"10.1073\/pnas.1604032113","article-title":"IL-33 ameliorates Alzheimer\u2019s disease-like pathology and cognitive decline.","volume":"113","author":"Fu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"112925","DOI":"10.1016\/j.yexcr.2021.112925","article-title":"miR-126 regulates angiogenesis in myocardial ischemia by targeting HIF-1\u03b1.","volume":"409","author":"Gao","year":"2021","journal-title":"Exp. Cell Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e167394","DOI":"10.1172\/jci.insight.167394","article-title":"Factor-inhibiting HIF (FIH) promotes lung cancer progression.","volume":"8","author":"Garc\u00eda-del R\u00edo","year":"2023","journal-title":"JCI Insight"},{"key":"B29","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1056\/NEJMoa031544","article-title":"Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia.","volume":"350","author":"Gibot","year":"","journal-title":"N. Engl. J. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"9","DOI":"10.7326\/0003-4819-141-1-200407060-00009","article-title":"Plasma level of a triggering receptor expressed on myeloid cells-1: Its diagnostic accuracy in patients with suspected sepsis.","volume":"141","author":"Gibot","year":"","journal-title":"Ann. Intern. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"28","DOI":"10.4274\/tji.galenos.2024.76598","article-title":"Peripheral expression of IL-6, TNF-\u03b1 and TGF-\u03b21 in Alzheimer\u2019s disease patients.","volume":"12","author":"G\u00fcven","year":"2024","journal-title":"TJI"},{"key":"B32","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3389\/fnagi.2018.00338","article-title":"Blood-Based kinase assessments in Alzheimer\u2019s disease.","volume":"10","author":"Hugon","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neurobiolaging.2005.02.009","article-title":"Alteration of protein kinase C conformation in red blood cells: A potential marker for Alzheimer\u2019s disease but not for Parkinson\u2019s disease.","volume":"27","author":"Janoshazi","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"B34","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1093\/cvr\/cvy018","article-title":"Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock.","volume":"114","author":"Jolly","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1038\/s41423-021-00733-5","article-title":"sTREM-1 is a specific biomarker of TREM-1 pathway activation.","volume":"18","author":"Jolly","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41514-024-00148-2","article-title":"Healthcare on the brink: Navigating the challenges of an aging society in the United States.","volume":"10","author":"Jones","year":"2024","journal-title":"NPJ Aging"},{"key":"B37","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3390\/biology15030213","article-title":"HIF-1\u03b1 as a central regulator of monocyte responses to hypoxia.","volume":"15","author":"Lampiasi","year":"2026","journal-title":"Biology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"111162","DOI":"10.1016\/j.brainresbull.2024.111162","article-title":"TREM1-Microglia crosstalk: Neurocognitive disorders.","volume":"220","author":"Li","year":"2025","journal-title":"Brain Res. Bull."},{"key":"B39","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jalz.2015.05.019","article-title":"Chronic hypoxia facilitates Alzheimer\u2019s disease through demethylation of \u03b3-secretase by downregulating DNA methyltransferase 3b.","volume":"12","author":"Liu","year":"2016","journal-title":"Alzheimers Dement."},{"key":"B40","doi-asserted-by":"publisher","first-page":"111652","DOI":"10.1016\/j.celrep.2022.111652","article-title":"Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature.","volume":"41","author":"Lombardi","year":"2022","journal-title":"Cell Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e2309957121","DOI":"10.1073\/pnas.2309957121","article-title":"Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment.","volume":"121","author":"Ma","year":"2024","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.3390\/cells10092340","article-title":"Regulation of the Hypoxia-Inducible Factor (HIF) by pro-inflammatory cytokines.","volume":"10","author":"Malkov","year":"2021","journal-title":"Cells"},{"key":"B43","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-\u03baB in inflammation and cancer.","volume":"22","author":"Mao","year":"2025","journal-title":"Cell Mol. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.exger.2009.02.007","article-title":"Glycogen-synthase kinase-3\u03b2 is decreased in peripheral blood mononuclear cells of patients with mild cognitive impairment.","volume":"44","author":"Marksteiner","year":"2009","journal-title":"Exp. Gerontol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12974-023-02793-y","article-title":"HIF1\u03b1-dependent hypoxia response in myeloid cells requires IRE1\u03b1.","volume":"20","author":"Mawambo","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"B46","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.cmet.2020.08.002","article-title":"The role of HIF in immunity and inflammation.","volume":"32","author":"McGettrick","year":"2020","journal-title":"Cell Metab."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4581","DOI":"10.3390\/ijms25094581","article-title":"The role of oxygen homeostasis and the HIF-1 factor in the development of neurodegeneration.","volume":"25","author":"Mitroshina","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.bbadis.2014.04.012","article-title":"Is Alzheimer\u2019s disease a systemic disease?","volume":"1842","author":"Morris","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"B49","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1007\/s00018-009-0141-0","article-title":"Contribution of hypoxia to Alzheimer\u2019s disease: Is HIF-1alpha a mediator of neurodegeneration?","volume":"66","author":"Ogunshola","year":"2009","journal-title":"Cell Mol. Life Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.immuni.2014.09.008","article-title":"HIF transcription factors, inflammation, and immunity.","volume":"41","author":"Palazon","year":"2014","journal-title":"Immunity"},{"key":"B51","doi-asserted-by":"publisher","first-page":"eabd5575","DOI":"10.1126\/sciadv.abd5575","article-title":"Single-cell peripheral immunoprofiling of Alzheimer\u2019s and Parkinson\u2019s diseases.","volume":"6","author":"Phongpreecha","year":"2020","journal-title":"Sci. Adv."},{"key":"B52","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s10787-024-01585-x","article-title":"Exploring the role of HIF-1\u03b1 on pathogenesis in Alzheimer\u2019s disease and potential therapeutic approaches.","volume":"33","author":"Porel","year":"2025","journal-title":"Inflammopharmacology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.7150\/thno.68304","article-title":"Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment.","volume":"12","author":"Rajeev","year":"2022","journal-title":"Theranostics"},{"key":"B54","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/nature06905","article-title":"NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha.","volume":"453","author":"Rius","year":"2008","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","first-page":"11941","DOI":"10.3390\/ijms252211941","article-title":"Neuroinflammatory biomarkers in Alzheimer\u2019s disease: From pathophysiology to clinical implications.","volume":"25","author":"Roveta","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3390\/jfmk7040087","article-title":"Age-Related changes in skeletal muscle oxygen utilization.","volume":"7","author":"Salvatore","year":"2022","journal-title":"J. Funct. Morphol. Kinesiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.3233\/JAD-180418","article-title":"TREM1 mRNA expression in leukocytes and cognitive function in Japanese patients with Alzheimer\u2019s disease.","volume":"64","author":"Sao","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"6285","DOI":"10.1038\/s41467-020-19111-2","article-title":"Cerebral small vessel disease genomics and its implications across the lifespan.","volume":"11","author":"Sargurupremraj","year":"2020","journal-title":"Nat. Commun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.4049\/jimmunol.2100418","article-title":"Knockout of factor-inhibiting HIF (Hif1an) in colon epithelium attenuates chronic colitis but does not reduce Colorectal cancer in mice.","volume":"208","author":"Sch\u00fctzhold","year":"2022","journal-title":"J. Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1172\/JCI31450","article-title":"Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology.","volume":"117","author":"Shaftel","year":"2007","journal-title":"J. Clin. Invest."},{"key":"B61","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s00018-024-05537-0","article-title":"HIF-1 and HIF-2 in cancer: Structure, regulation, and therapeutic prospects.","volume":"82","author":"Shi","year":"2025","journal-title":"Cell Mol. Life Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3390\/cells8050384","article-title":"Protein Hydroxylation by Hypoxia-Inducible Factor (HIF) hydroxylases: Unique or ubiquitous?","volume":"8","author":"Strowitzki","year":"2019","journal-title":"Cells"},{"key":"B63","doi-asserted-by":"publisher","first-page":"18727","DOI":"10.1073\/pnas.0606298103","article-title":"Hypoxia facilitates Alzheimer\u2019s disease pathogenesis by up-regulating BACE1 gene expression.","volume":"103","author":"Sun","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B64","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.pharmthera.2017.02.043","article-title":"TREM-1 and its potential ligands in non-infectious diseases: From biology to clinical perspectives.","volume":"177","author":"Tammaro","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1073971","DOI":"10.3389\/fimmu.2022.1073971","article-title":"Emerging role of hypoxia-inducible factor-1\u03b1 in inflammatory autoimmune diseases: A comprehensive review.","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1.","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2174\/1573403X19666230330105259","article-title":"Regulation of HIF-1 by MicroRNAs in various cardiovascular diseases.","volume":"19","author":"Tarhriz","year":"2023","journal-title":"Curr. Cardiol. Rev."},{"key":"B68","doi-asserted-by":"publisher","first-page":"4055","DOI":"10.1113\/jphysiol.2008.157669","article-title":"Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation.","volume":"586","author":"Taylor","year":"2008","journal-title":"J. Physiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"11162","DOI":"10.1038\/s41598-024-61493-6","article-title":"Cholesterol accumulation impairs HIF-1\u03b1-dependent immunometabolic reprogramming of LPS-stimulated macrophages by upregulating the NRF2 pathway.","volume":"14","author":"Ting","year":"2024","journal-title":"Sci. Rep."},{"key":"B70","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.14336\/AD.2024.1174","article-title":"Neuroinflammation as a link in parkinson\u2019s and alzheimer\u2019s diseases: A systematic review and meta-analysis.","volume":"16","author":"Tylutka","year":"2024","journal-title":"Aging Dis."},{"key":"B71","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1093\/jb\/mvz067","article-title":"Post-transcriptional regulation of inflammation by RNA-binding proteins via cis-elements of mRNAs.","volume":"166","author":"Uchida","year":"2019","journal-title":"J. Biochem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1089\/ars.2022.0003","article-title":"The asparagine hydroxylase FIH: A unique oxygen sensor.","volume":"37","author":"Volkova","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"B73","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.jocn.2013.08.017","article-title":"Peripheral expression of MAPK pathways in Alzheimer\u2019s and Parkinson\u2019s diseases.","volume":"21","author":"Wang","year":"2014","journal-title":"J. Clin. Neurosci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"949","DOI":"10.3233\/JAD-201448","article-title":"Role of hypoxia inducible factor-1\u03b1 in Alzheimer\u2019s disease.","volume":"80","author":"Wang","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"B75","volume-title":"Dementia.","year":"2025"},{"key":"B76","doi-asserted-by":"publisher","first-page":"e202410438","DOI":"10.1002\/anie.202410438","article-title":"A small-molecule inhibitor of factor inhibiting HIF binding to a tyrosine-flip pocket for the treatment of obesity.","volume":"63","author":"Wu","year":"2024","journal-title":"Angew Chem. Int. Ed"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1038\/s12276-021-00714-8","article-title":"Single-cell RNA sequencing reveals B cell-related molecular biomarkers for Alzheimer\u2019s disease.","volume":"53","author":"Xiong","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"645666","DOI":"10.3389\/fimmu.2021.645666","article-title":"Single-Cell RNA sequencing of peripheral blood reveals immune cell signatures in Alzheimer\u2019s disease.","volume":"12","author":"Xu","year":"2021","journal-title":"Front. Immunol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"798","DOI":"10.3390\/cells12050798","article-title":"Transcriptional response to hypoxia: The role of HIF-1-associated co-regulators.","volume":"12","author":"Yfantis","year":"2023","journal-title":"Cells"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1111\/febs.16344","article-title":"Lipid metabolism and Alzheimer\u2019s disease: Clinical evidence, mechanistic link and therapeutic promise.","volume":"290","author":"Yin","year":"2023","journal-title":"FEBS J."},{"key":"B81","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s11658-024-00682-7","article-title":"Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: Implications for cellular adaptation and therapeutic strategies in cancer.","volume":"30","author":"Zhang","year":"2025","journal-title":"Cell Mol. Biol. Lett."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1831919\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:00:18Z","timestamp":1780466418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1831919\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":81,"alternative-id":["10.3389\/fnagi.2026.1831919"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1831919","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1831919"}}