{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:51Z","timestamp":1785431451997,"version":"3.56.0"},"reference-count":130,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01HL136706"],"award-info":[{"award-number":["R01HL136706"]}]},{"name":"NIH","award":["R21AI171574"],"award-info":[{"award-number":["R21AI171574"]}]},{"name":"NIH","award":["R21AI185651"],"award-info":[{"award-number":["R21AI185651"]}]},{"name":"National Science Foundation","award":["1722630"],"award-info":[{"award-number":["1722630"]}]},{"award":["1722630"],"award-info":[{"award-number":["1722630"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>SARS-CoV-2 infection leads to extrapulmonary complications in multiple organs, including the brain, both in the short-term and long-term. The neurological manifestation of SARS-CoV-2 infection ranges from benign signs like loss of smell and loss of taste to severe complications like encephalitis, stroke, and exacerbation of Alzheimer\u2019s disease (AD) progression. Pericytes are mural cells of the brain vasculature that help maintain the blood\u2013brain barrier (BBB), regulate cerebral blood flow (CBF), modulate neuroinflammation, and clear toxic materials, including amyloid beta. Pericytes express ACE2, the receptor for SARS-CoV-2, and therefore may be targeted by either direct virus infection or virus-induced inflammatory cytokines induced by the virus in the brain. To further study the effects of SARS-CoV-2 on pericytes and BBB integrity, the long-term effects of SARS-CoV-2 infection on brain pericytes, inflammation, and other neuropathological complications were analyzed in mice. K18 (human ACE2 transgenic) mice were infected with 103 PFU of SARS-CoV-2 (delta strain), and the brains were analyzed at 6, 14, and 30 days post-infection (dpi). A significant reduction in the weight of infected mice was observed by 6 dpi. Viral nucleocapsid protein and infectious SARS-CoV-2 were observed in the brains of all mice by 6 dpi, and in some mice by 14 dpi, but not at 30 dpi. This observation suggests viral neurotropism with subsequent clearance at later timepoints. Despite virus clearance, the levels of inflammatory mediators, including TNF-\u03b1 and IFN-\u03b3 were significantly elevated up to 30 dpi. We also observed a significant reduction in the level of brain pericytes by 14 dpi up to 30 dpi. Importantly, an increase was observed in the level of Friend Leukemia Integration 1 (FLI-1), a transcription factor known to promote pericyte cell death, from 14 dpi up to 30 dpi. The level of amyloid beta 1\u201342 was elevated in the brain of infected mice at 6 dpi, and this was maintained up to 30 dpi, and there was a decrease in neuronal density from 14 to 30 dpi. Furthermore, we observed an increased expression of Alzheimer\u2019s disease (AD)-associated genes like PSEN1, BACE1, and APP. Furthermore, there was increased activation of several neurodegenerative pathways, including \u201cG alpha (z) signaling pathway\u201d, \u201cApelin muscle signaling pathway\u201d, and \u201cG beta-gamma (G\u03b2\u03b3) signaling\u201d, in the brains of infected mice compared to control mice. Collectively, the observed neuropathology and unique molecular markers of neurodegenerative disease progression provide a novel mechanism by which COVID-19 may promote dementia\/AD by contributing to pericyte loss and BBB dysfunction during infection.<\/jats:p>","DOI":"10.3390\/v18070783","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:44:02Z","timestamp":1784544242000},"page":"783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroinflammation, Pericyte Dysfunction, and Alzheimer\u2019s Disease-Associated Gene Expression and Pathway Activation in the Brain of SARS-CoV-2-Infected Mice"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2293-1008","authenticated-orcid":false,"given":"Akinkunmi O.","family":"Lawal","sequence":"first","affiliation":[{"name":"Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu B.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vignesh","family":"Karnik","sequence":"additional","affiliation":[{"name":"Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9441-9405","authenticated-orcid":false,"given":"Hongkuan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-5993","authenticated-orcid":false,"given":"Saravanan","family":"Thangamani","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9584-8212","authenticated-orcid":false,"given":"Paul T.","family":"Massa","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Department of Neurology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-8572","authenticated-orcid":false,"given":"Guirong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","unstructured":"(2024, March 26). 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