{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:40:27Z","timestamp":1793094027823,"version":"4.5.0"},"reference-count":118,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016958","name":"National Institutes of Health Office of Research Infrastructure Programs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007875","name":"Tulane University","doi-asserted-by":"publisher","award":["SCR_008167"],"award-info":[{"award-number":["SCR_008167"]}],"id":[{"id":"10.13039\/100007875","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.ajpath.2025.03.011","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T02:34:15Z","timestamp":1744943655000},"page":"2075-2087","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in Coronavirus Disease 2019 and Alzheimer Disease"],"prefix":"10.1016","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1648-2422","authenticated-orcid":false,"given":"Meredith G.","family":"Mayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-3776","authenticated-orcid":false,"given":"Tracy","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2025.03.011_bib1","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1002\/alz.13809","article-title":"2024 Alzheimer's disease facts and figures","volume":"20","year":"2024","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.ajpath.2025.03.011_bib2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.3389\/fnhum.2019.00464","article-title":"Neuroinflammation and white matter alterations in obesity assessed by diffusion basis spectrum imaging","volume":"13","author":"Samara","year":"2020","journal-title":"Front Hum Neurosci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12974-016-0666-8","article-title":"High-fat diet feeding differentially affects the development of inflammation in the central nervous system","volume":"13","author":"Guillemot-Legris","year":"2016","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.ajpath.2025.03.011_bib5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/TA.0000000000000468","article-title":"Clinical evidence of inflammation driving secondary brain injury: a systematic review","volume":"78","author":"Hinson","year":"2015","journal-title":"J Trauma Acute Care Surg"},{"key":"10.1016\/j.ajpath.2025.03.011_bib6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s12974-021-02264-2","article-title":"Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury","volume":"18","author":"Lassar\u00e9n","year":"2021","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.ajpath.2025.03.011_bib7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/jcbfm.2014.75","article-title":"Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits","volume":"34","author":"Aungst","year":"2014","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.1016\/j.ajpath.2025.03.011_bib8","article-title":"Northwestern University successful clinical response in pneumonia therapy I: prolonged exposure to lung-derived cytokines is associated with activation of microglia in patients with COVID-19","volume":"9","author":"Grant","year":"2024","journal-title":"JCI Insight"},{"key":"10.1016\/j.ajpath.2025.03.011_bib9","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1523\/JNEUROSCI.1740-17.2018","article-title":"Long-term neuroinflammation induced by influenza A virus infection and the impact on hippocampal neuron morphology and function","volume":"38","author":"Hosseini","year":"2018","journal-title":"J Neurosci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib10","doi-asserted-by":"crossref","DOI":"10.1080\/22221751.2022.2164215","article-title":"Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study","volume":"12","author":"Hwang","year":"2023","journal-title":"Emerg Microbes Infect"},{"key":"10.1016\/j.ajpath.2025.03.011_bib11","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-54334-7","article-title":"Outcome of SARS-CoV-2 reinfection depends on genetic background in female mice","volume":"15","author":"Singh","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib12","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.3390\/ijerph20032146","article-title":"Links between COVID-19 and Alzheimer's disease-what do we already know?","volume":"20","author":"Rudnicka-Dro\u017cak","year":"2023","journal-title":"Int J Environ Res Public Health"},{"key":"10.1016\/j.ajpath.2025.03.011_bib13","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1002\/alz.12558","article-title":"Alzheimer's-like signaling in brains of COVID-19 patients","volume":"18","author":"Reiken","year":"2022","journal-title":"Alzheimers Dementia"},{"key":"10.1016\/j.ajpath.2025.03.011_bib14","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3233\/JAD-220717","article-title":"Association of COVID-19 with new-onset alzheimer's disease","volume":"89","author":"Wang","year":"2022","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.ajpath.2025.03.011_bib15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3233\/ADR-220090","article-title":"The effects of SARS-CoV-2 infection on the cognitive functioning of patients with pre-existing dementia","volume":"7","author":"Dubey","year":"2023","journal-title":"J Alzheimers Dis Rep"},{"key":"10.1016\/j.ajpath.2025.03.011_bib16","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1038\/s41467-022-29440-z","article-title":"Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates","volume":"13","author":"Rutkai","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib17","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1038\/s41379-021-00793-y","article-title":"Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience","volume":"34","author":"Bryce","year":"2021","journal-title":"Mod Pathology"},{"key":"10.1016\/j.ajpath.2025.03.011_bib18","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S1474-4422(20)30308-2","article-title":"Neuropathology of patients with COVID-19 in Germany: a post-mortem case series","volume":"19","author":"Matschke","year":"2020","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib19","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1038\/s41467-022-30836-0","article-title":"Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records","volume":"13","author":"Thompson","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib20","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/s41591-022-01909-w","article-title":"Symptoms and risk factors for long COVID in non-hospitalized adults","volume":"28","author":"Subramanian","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.ajpath.2025.03.011_bib21","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1096\/fj.15-275834","article-title":"IFN-gamma promotes tau phosphorylation without affecting mature tangles","volume":"29","author":"Li","year":"2015","journal-title":"FASEB J"},{"key":"10.1016\/j.ajpath.2025.03.011_bib22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.brainres.2010.10.053","article-title":"Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP\/PS1 transgenic mouse brains","volume":"1368","author":"Shi","year":"2011","journal-title":"Brain Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/1742-2094-9-106","article-title":"Tumor necrosis factor-alpha synthesis inhibitor 3,6'-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer's disease","volume":"9","author":"Tweedie","year":"2012","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.ajpath.2025.03.011_bib24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yexcr.2004.01.002","article-title":"Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5\/p35 pathway","volume":"295","author":"Quintanilla","year":"2004","journal-title":"Exp Cell Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/0197-4580(96)00104-2","article-title":"In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis","volume":"17","author":"Sheng","year":"1996","journal-title":"Neurobiol Aging"},{"key":"10.1016\/j.ajpath.2025.03.011_bib26","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41593-024-01576-9","article-title":"Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment","volume":"27","author":"Greene","year":"2024","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib27","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1056\/NEJMc2033369","article-title":"Microvascular injury in the brains of patients with Covid-19","volume":"384","author":"Lee","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ajpath.2025.03.011_bib28","doi-asserted-by":"crossref","DOI":"10.1111\/bpa.12997","article-title":"COVID-19-related neuropathology and microglial activation in elderly with and without dementia","volume":"31","author":"Poloni","year":"2021","journal-title":"Brain Pathol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41531-023-00467-3","article-title":"Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei","volume":"9","author":"Emmi","year":"2023","journal-title":"NPJ Parkinsons Dis"},{"key":"10.1016\/j.ajpath.2025.03.011_bib30","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s40478-023-01566-1","article-title":"SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature","volume":"11","author":"Lebrun","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib31","doi-asserted-by":"crossref","first-page":"H1241","DOI":"10.1152\/ajpheart.2001.280.3.H1241","article-title":"Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression","volume":"280","author":"Huber","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib32","article-title":"Peripheral inflammation promotes brain tau transmission via disrupting blood-brain barrier","volume":"40","author":"Liu","year":"2020","journal-title":"Biosci Rep"},{"key":"10.1016\/j.ajpath.2025.03.011_bib33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bbrc.2021.04.014","article-title":"Exploring the changes of brain immune microenvironment in Alzheimer's disease based on PANDA algorithm combined with blood brain barrier injury-related genes","volume":"557","author":"Lu","year":"2021","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib34","doi-asserted-by":"crossref","DOI":"10.1177\/1759091417719201","article-title":"Peripheral inflammation, apolipoprotein E4, and amyloid-beta interact to induce cognitive and cerebrovascular dysfunction","volume":"9","author":"Marottoli","year":"2017","journal-title":"ASN Neuro"},{"key":"10.1016\/j.ajpath.2025.03.011_bib35","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s40478-021-01253-z","article-title":"Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer's disease","volume":"9","author":"Xie","year":"2021","journal-title":"Acta Neuropathol Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib36","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbi.2009.09.001","article-title":"Minimal penetration of lipopolysaccharide across the murine blood-brain barrier","volume":"24","author":"Banks","year":"2010","journal-title":"Brain Behavior Immun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib37","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1124\/jpet.122.001380","article-title":"Transport of the proinflammatory chemokines C-C motif chemokine ligand 2 (MCP-1) and C-C motif chemokine ligand 5 (RANTES) across the intact mouse blood-brain barrier is inhibited by heparin and eprodisate and increased with systemic inflammation","volume":"384","author":"Quaranta","year":"2023","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.ajpath.2025.03.011_bib38","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ajpath.2025.03.011_bib39","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.ajpath.2025.03.011_bib40","doi-asserted-by":"crossref","first-page":"972","DOI":"10.2174\/1567205017666201130092427","article-title":"The association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer's disease","volume":"17","author":"Culjak","year":"2020","journal-title":"Curr Alzheimer Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib41","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/ggi.12783","article-title":"Peripheral cytokines, C-X-C motif ligand10 and interleukin-13, are associated with Malaysian Alzheimer's disease","volume":"17","author":"Mohd Hasni","year":"2017","journal-title":"Geriatr Gerontol Int"},{"key":"10.1016\/j.ajpath.2025.03.011_bib42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.14336\/AD.2016.1017","article-title":"Role of pro-inflammatory cytokines and vitamin D in probable Alzheimer's disease with depression","volume":"8","author":"Banerjee","year":"2017","journal-title":"Aging Dis"},{"key":"10.1016\/j.ajpath.2025.03.011_bib43","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.expneurol.2004.08.008","article-title":"Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model of the human blood-brain barrier","volume":"190","author":"Wong","year":"2004","journal-title":"Exp Neurol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib44","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01476-14","article-title":"Viral pathogen-associated molecular patterns regulate blood-brain barrier integrity via competing innate cytokine signals","volume":"5","author":"Daniels","year":"2014","journal-title":"mBio"},{"key":"10.1016\/j.ajpath.2025.03.011_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2020.146647","article-title":"Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-alpha) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model","volume":"1730","author":"Voirin","year":"2020","journal-title":"Brain Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib46","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000001076","article-title":"New BBB model reveals that IL-6 blockade suppressed the BBB disorder, preventing onset of NMOSD","volume":"8","author":"Takeshita","year":"2021","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"10.1016\/j.ajpath.2025.03.011_bib47","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1074\/jbc.M117.815381","article-title":"The EPAC-Rap1 pathway prevents and reverses cytokine-induced retinal vascular permeability","volume":"293","author":"Ramos","year":"2018","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2025.03.011_bib48","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aba2940","article-title":"A venous-specific purinergic signaling cascade initiated by pannexin 1 regulates TNFalpha-induced increases in endothelial permeability","volume":"14","author":"Maier-Begandt","year":"2021","journal-title":"Sci Signal"},{"key":"10.1016\/j.ajpath.2025.03.011_bib49","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.644733","article-title":"Endothelial dysfunction and impaired neurovascular coupling responses precede cognitive impairment in a mouse model of geriatric sepsis","volume":"13","author":"Csipo","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2019.101192","article-title":"Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice","volume":"24","author":"Tarantini","year":"2019","journal-title":"Redox Biol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib51","doi-asserted-by":"crossref","DOI":"10.1111\/acel.12731","article-title":"Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice","volume":"17","author":"Tarantini","year":"2018","journal-title":"Aging Cell"},{"key":"10.1016\/j.ajpath.2025.03.011_bib52","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/S0002-9440(10)61204-7","article-title":"Tissue factor-dependent coagulation is preferentially up-regulated within arterial branching areas in a baboon model of Escherichia coli sepsis","volume":"167","author":"Lupu","year":"2005","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib53","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1172\/JCI110945","article-title":"Cultured human endothelial cells generate tissue factor in response to endotoxin","volume":"71","author":"Colucci","year":"1983","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ajpath.2025.03.011_bib54","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1073\/pnas.1914593117","article-title":"Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain","volume":"117","author":"Welikovitch","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2025.03.011_bib55","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1161\/01.RES.74.6.1141","article-title":"Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells","volume":"74","author":"Griendling","year":"1994","journal-title":"Circ Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib56","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1172\/JCI118623","article-title":"Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH\/NADPH oxidase activation: contribution to alterations of vasomotor tone","volume":"97","author":"Rajagopalan","year":"1996","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ajpath.2025.03.011_bib57","doi-asserted-by":"crossref","first-page":"876","DOI":"10.3390\/ijms19030876","article-title":"Within the brain: the renin angiotensin system","volume":"19","author":"Jackson","year":"2018","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib58","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1152\/physrev.00023.2016","article-title":"The ACE2\/angiotensin-(1-7)\/MAS axis of the renin-angiotensin system: focus on angiotensin-(1-7)","volume":"98","author":"Santos","year":"2018","journal-title":"Physiol Rev"},{"key":"10.1016\/j.ajpath.2025.03.011_bib59","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1161\/HYPERTENSIONAHA.106.084848","article-title":"Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells","volume":"50","author":"Sampaio","year":"2007","journal-title":"Hypertension"},{"key":"10.1016\/j.ajpath.2025.03.011_bib60","doi-asserted-by":"crossref","first-page":"8258","DOI":"10.1073\/pnas.1432869100","article-title":"Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas","volume":"100","author":"Santos","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2025.03.011_bib61","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1161\/01.HYP.0000251865.35728.2f","article-title":"Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways","volume":"49","author":"Sampaio","year":"2007","journal-title":"Hypertension"},{"key":"10.1016\/j.ajpath.2025.03.011_bib62","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/00005344-200007000-00015","article-title":"Evidence that prostaglandins mediate the antihypertensive actions of angiotensin-(1-7) during chronic blockade of the renin-angiotensin system","volume":"36","author":"Iyer","year":"2000","journal-title":"J Cardiovasc Pharmacol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib63","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1210\/en.2011-2031","article-title":"Angiotensin-(1-7) administration reduces oxidative stress in diabetic bone marrow","volume":"153","author":"Mordwinkin","year":"2012","journal-title":"Endocrinology"},{"key":"10.1016\/j.ajpath.2025.03.011_bib64","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1111\/j.1476-5381.2012.02105.x","article-title":"Suppressing inflammation by inhibiting the NF-kappaB pathway contributes to the neuroprotective effect of angiotensin-(1-7) in rats with permanent cerebral ischaemia","volume":"167","author":"Jiang","year":"2012","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib65","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.3390\/ijms22041687","article-title":"Protein expression of angiotensin-converting enzyme 2 (ACE2) is upregulated in brains with Alzheimer's disease","volume":"22","author":"Ding","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib66","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1093\/gerona\/glac083","article-title":"Dysregulation of ACE-1 in normal aging and the early stages of Alzheimer's disease","volume":"77","author":"MacLachlan","year":"2022","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib67","doi-asserted-by":"crossref","first-page":"5847","DOI":"10.1007\/s12035-017-0805-y","article-title":"Paracrine and intracrine angiotensin 1-7\/Mas receptor axis in the substantia nigra of rodents, monkeys, and humans","volume":"55","author":"Costa-Besada","year":"2018","journal-title":"Mol Neurobiology"},{"key":"10.1016\/j.ajpath.2025.03.011_bib68","doi-asserted-by":"crossref","first-page":"8188","DOI":"10.1007\/s12035-018-0966-3","article-title":"Stimulation of ACE2\/ANG(1-7)\/Mas axis by diminazene ameliorates Alzheimer's disease in the D-galactose-ovariectomized rat model: role of PI3K\/Akt pathway","volume":"55","author":"Kamel","year":"2018","journal-title":"Mol Neurobiol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib69","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110902","article-title":"An integrated model for Gpr124 function in Wnt7a\/b signaling among vertebrates","volume":"39","author":"America","year":"2022","journal-title":"Cell Rep"},{"key":"10.1016\/j.ajpath.2025.03.011_bib70","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nm.4309","article-title":"Gpr124 is essential for blood-brain barrier integrity in central nervous system disease","volume":"23","author":"Chang","year":"2017","journal-title":"Nat Med"},{"key":"10.1016\/j.ajpath.2025.03.011_bib71","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1093\/brain\/awae031","article-title":"Engineered Wnt7a ligands rescue blood-brain barrier and cognitive deficits in a COVID-19 mouse model","volume":"147","author":"Trevino","year":"2024","journal-title":"Brain"},{"key":"10.1016\/j.ajpath.2025.03.011_bib72","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.celrep.2018.09.045","article-title":"A RECK-WNT7 receptor-ligand interaction enables isoform-specific regulation of Wnt bioavailability","volume":"25","author":"Vallon","year":"2018","journal-title":"Cell Rep"},{"key":"10.1016\/j.ajpath.2025.03.011_bib73","article-title":"Pro-inflammatory role of Wnt\/beta-catenin signaling in endothelial dysfunction","volume":"9","author":"Wadey","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"10.1016\/j.ajpath.2025.03.011_bib74","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2019.05.001","article-title":"Type I interferon signaling, regulation and gene stimulation in chronic virus infection","volume":"43","author":"Lukhele","year":"2019","journal-title":"Semin Immunol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib75","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib76","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaa2630","article-title":"Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation","volume":"347","author":"Liu","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.ajpath.2025.03.011_bib77","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.70992","article-title":"Wnt signaling mediates acquisition of blood-brain barrier properties in naive endothelium derived from human pluripotent stem cells","volume":"10","author":"Gastfriend","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.ajpath.2025.03.011_bib78","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1073\/pnas.0805165106","article-title":"Wnt\/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis","volume":"106","author":"Daneman","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2025.03.011_bib79","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2022.895429","article-title":"Endothelial beta-catenin deficiency causes blood-brain barrier breakdown via enhancing the paracellular and transcellular permeability","volume":"15","author":"Hussain","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib80","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12974-024-03261-x","article-title":"Compromised endothelial Wnt\/beta-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia","volume":"21","author":"Huang","year":"2024","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.ajpath.2025.03.011_bib81","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1093\/brain\/awac236","article-title":"Activation of Wnt\/beta-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease","volume":"145","author":"Wang","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.ajpath.2025.03.011_bib82","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11934","article-title":"Alzheimer's disease neuroimaging I: early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis","volume":"7","author":"Iturria-Medina","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40035-023-00388-4","article-title":"Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer's disease","volume":"13","author":"Zhang","year":"2024","journal-title":"Transl Neurodegener"},{"key":"10.1016\/j.ajpath.2025.03.011_bib84","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.ajpath.2025.03.011_bib85","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41419-024-06639-0","article-title":"Endothelial DR6 in blood-brain barrier malfunction in Alzheimer's disease","volume":"15","author":"Huang","year":"2024","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.ajpath.2025.03.011_bib86","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12987-024-00533-9","article-title":"SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway","volume":"21","author":"Yamada","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"10.1016\/j.ajpath.2025.03.011_bib87","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00401-023-02616-7","article-title":"Inflammation and the pathological progression of Alzheimer's disease are associated with low circulating choline levels","volume":"146","author":"Judd","year":"2023","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib88","doi-asserted-by":"crossref","first-page":"16514","DOI":"10.1074\/jbc.270.28.16514","article-title":"NF-kappa B activation by interleukin-1 (IL-1) requires an IL-1 receptor-associated protein kinase activity","volume":"270","author":"Croston","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2025.03.011_bib89","doi-asserted-by":"crossref","first-page":"141","DOI":"10.12659\/MSMBR.903910","article-title":"TNF-alpha promotes invasion and metastasis via NF-kappa B pathway in oral squamous cell carcinoma","volume":"23","author":"Tang","year":"2017","journal-title":"Med Sci Monit Basic Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib90","article-title":"NF-kappaB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.ajpath.2025.03.011_bib91","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0304-3940(94)90933-4","article-title":"Penetration of interleukin-6 across the murine blood-brain barrier","volume":"179","author":"Banks","year":"1994","journal-title":"Neurosci Lett"},{"key":"10.1016\/j.ajpath.2025.03.011_bib92","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0165-5728(93)90027-V","article-title":"Murine tumor necrosis factor alpha is transported from blood to brain in the mouse","volume":"47","author":"Gutierrez","year":"1993","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib93","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1159\/000288265","article-title":"Ovine proinflammatory cytokines cross the murine blood-brain barrier by a common saturable transport mechanism","volume":"17","author":"Threlkeld","year":"2010","journal-title":"Neuroimmunomodulation"},{"key":"10.1016\/j.ajpath.2025.03.011_bib94","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1159\/000439214","article-title":"Alterations of the neuroinflammatory markers IL-6 and TRAIL in Alzheimer's disease","volume":"5","author":"Wu","year":"2015","journal-title":"Dement Geriatr Cogn Dis Extra"},{"key":"10.1016\/j.ajpath.2025.03.011_bib95","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1212\/WNL.0b013e3181b6bb95","article-title":"Systemic inflammation and disease progression in Alzheimer disease","volume":"73","author":"Holmes","year":"2009","journal-title":"Neurology"},{"key":"10.1016\/j.ajpath.2025.03.011_bib96","doi-asserted-by":"crossref","first-page":"4264","DOI":"10.1007\/s12035-024-04551-4","article-title":"Neuroinflammation in severe COVID-19: the dynamics of inflammatory and brain injury markers during hospitalization","volume":"62","author":"Neves","year":"2025","journal-title":"Mol Neurobiol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib97","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.3390\/cells10092262","article-title":"Neuropathology and inflammatory cell characterization in 10 autoptic COVID-19 brains","volume":"10","author":"Colombo","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.ajpath.2025.03.011_bib98","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.86333","article-title":"Recapitulation of pathophysiological features of AD in SARS-CoV-2-infected subjects","volume":"12","author":"Griggs","year":"2023","journal-title":"Elife"},{"key":"10.1016\/j.ajpath.2025.03.011_bib100","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3390\/v16010100","article-title":"Investigating the potential shared molecular mechanisms between COVID-19 and Alzheimer's disease via transcriptomic analysis","volume":"16","author":"Fan","year":"2024","journal-title":"Viruses"},{"key":"10.1016\/j.ajpath.2025.03.011_bib101","article-title":"Clinical and CSF single-cell profiling of post-COVID-19 cognitive impairment","volume":"5","author":"Hu","year":"2024","journal-title":"Cell Rep Med"},{"key":"10.1016\/j.ajpath.2025.03.011_bib102","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S1074-7613(01)00226-6","article-title":"Inhibition of IFN-gamma signaling by an Epstein-Barr virus immediate-early protein","volume":"15","author":"Morrison","year":"2001","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.03.011_bib103","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1097\/01.WCB.0000080703.47016.B6","article-title":"Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat","volume":"23","author":"Veldhuis","year":"2003","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.1016\/j.ajpath.2025.03.011_bib104","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1097\/01.WCB.0000080701.47016.24","article-title":"Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption","volume":"23","author":"Veldhuis","year":"2003","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.1016\/j.ajpath.2025.03.011_bib105","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.1128\/JVI.03149-13","article-title":"Enhancement of blood-brain barrier permeability and reduction of tight junction protein expression are modulated by chemokines\/cytokines induced by rabies virus infection","volume":"88","author":"Chai","year":"2014","journal-title":"J Virol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib106","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.bbi.2014.02.020","article-title":"The pro-inflammatory cytokine interferon-gamma is an important driver of neuropathology and behavioural sequelae in experimental pneumococcal meningitis","volume":"40","author":"Too","year":"2014","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib107","doi-asserted-by":"crossref","first-page":"6078","DOI":"10.1038\/s41467-020-19967-4","article-title":"Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates","volume":"11","author":"Fahlberg","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib108","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.953502","article-title":"Low baseline IFN-gamma response could predict hospitalization in COVID-19 patients","volume":"13","author":"Cremoni","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib109","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3390\/biomedicines10050934","article-title":"The evolution of blood cell phenotypes, intracellular and plasma cytokines and morphological changes in critically ill COVID-19 patients","volume":"10","author":"Berghall","year":"2022","journal-title":"Biomedicines"},{"key":"10.1016\/j.ajpath.2025.03.011_bib110","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.139834","article-title":"Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease","volume":"5","author":"Zhao","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.ajpath.2025.03.011_bib111","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1089\/107999000312342","article-title":"Expression of IFN-gamma in cerebrovascular endothelial cells from aged mice","volume":"20","author":"Wei","year":"2000","journal-title":"J Interferon Cytokine Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib112","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbi.2017.08.020","article-title":"Interferon-[gamma] mediated signaling in the brain endothelium is critical for inflammation-induced aversion","volume":"67","author":"Fritz","year":"2018","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.ajpath.2025.03.011_bib113","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1097\/JCP.0000000000000840","article-title":"Acetyl cholinesterase inhibitors and cell-derived peripheral inflammatory cytokines in early stages of Alzheimer's disease","volume":"38","author":"Kokras","year":"2018","journal-title":"J Clin Psychopharmacol"},{"key":"10.1016\/j.ajpath.2025.03.011_bib114","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10072-006-0562-6","article-title":"Increased intrathecal TGF-beta1, but not IL-12, IFN-gamma and IL-10 levels in Alzheimer's disease patients","volume":"27","author":"Rota","year":"2006","journal-title":"Neurol Sci"},{"key":"10.1016\/j.ajpath.2025.03.011_bib115","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1089\/jir.2013.0085","article-title":"IFN-gamma and TNF-alpha are involved during Alzheimer disease progression and correlate with nitric oxide production: a study in Algerian patients","volume":"34","author":"Belkhelfa","year":"2014","journal-title":"J Interferon Cytokine Res"},{"key":"10.1016\/j.ajpath.2025.03.011_bib116","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1093\/brain\/awab094","article-title":"Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer's disease","volume":"144","author":"Asby","year":"2021","journal-title":"Brain"},{"key":"10.1016\/j.ajpath.2025.03.011_bib117","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2022.104175","article-title":"Impaired type I interferon signaling activity implicated in the peripheral blood transcriptome of preclinical Alzheimer's disease","volume":"82","author":"Song","year":"2022","journal-title":"EBioMedicine"},{"key":"10.1016\/j.ajpath.2025.03.011_bib118","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.immuni.2020.12.011","article-title":"Neurological manifestations of COVID-19 feature T cell exhaustion and dedifferentiated monocytes in cerebrospinal fluid","volume":"54","author":"Heming","year":"2021","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.03.011_bib119","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1172\/JCI133737","article-title":"Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease","volume":"130","author":"Roy","year":"2020","journal-title":"J Clin Invest"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000294402500118X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000294402500118X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T03:42:32Z","timestamp":1763610152000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S000294402500118X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":118,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["S000294402500118X"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2025.03.011","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in Coronavirus Disease 2019 and Alzheimer Disease","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2025.03.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Society for Investigative Pathology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}