{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:03:59Z","timestamp":1791299039248,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The mechanisms that lead to cognitive impairment associated with COVID\u201019 are not well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Brain lysates from control and COVID\u201019 patients were analyzed for oxidative stress and inflammatory signaling pathway markers, and measurements of Alzheimer\u2019s disease (AD)\u2010linked signaling biochemistry. Post\u2010translational modifications of the ryanodine receptor\/calcium (Ca2<jats:sup>+<\/jats:sup>) release channels (RyR) on the endoplasmic reticuli (ER), known to be linked to AD, were also measured by co\u2010immunoprecipitation\/immunoblotting of the brain lysates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We provide evidence linking SARS\u2010CoV\u20102 infection to activation of TGF\u2010\u03b2 signaling and oxidative overload. The neuropathological pathways causing tau hyperphosphorylation typically associated with AD were also shown to be activated in COVID\u201019 patients. RyR2 in COVID\u201019 brains demonstrated a \u201cleaky\u201d phenotype, which can promote cognitive and behavioral defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>COVID\u201019 neuropathology includes AD\u2010like features and leaky RyR2 channels could be a therapeutic target for amelioration of some cognitive defects associated with SARS\u2010CoV\u20102 infection and long COVID.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12558","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T07:04:26Z","timestamp":1643871866000},"page":"955-965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":170,"title":["Alzheimer's\u2010like signaling in brains of COVID\u201019 patients"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-3574","authenticated-orcid":false,"given":"Steve","family":"Reiken","sequence":"first","affiliation":[{"name":"Department of Physiology and Cellular Biophysics Clyde and Helen Wu Center for Molecular Cardiology Columbia University Vagelos College of Physicians and Surgeons  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Sittenfeld","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics Clyde and Helen Wu Center for Molecular Cardiology Columbia University Vagelos College of Physicians and Surgeons  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikel","family":"Dridi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics Clyde and Helen Wu Center for Molecular Cardiology Columbia University Vagelos College of 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