{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:57:23Z","timestamp":1782997043934,"version":"3.54.5"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Department of Defense\/Uniformed Services University Brain Tissue Repository and Neuropathology Program","award":["HU00012120007"],"award-info":[{"award-number":["HU00012120007"]}]},{"DOI":"10.13039\/100007188","name":"Uniformed Services University","doi-asserted-by":"publisher","award":["312159-1.00-66531"],"award-info":[{"award-number":["312159-1.00-66531"]}],"id":[{"id":"10.13039\/100007188","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The brain of a 58-year-old woman was included as a civilian control in an ongoing autopsy study of military traumatic brain injury (TBI). The woman died due to a polysubstance drug overdose, with Coronavirus Disease 2019 (COVID-19) serving as a contributing factor. Immunohistochemical stains for \u03b2-amyloid (A\u03b2), routinely performed for the TBI study, revealed numerous, unusual neocortical A\u03b2 deposits. We investigated the autopsied brains of 10 additional young patients (&amp;lt;60\u2009years old) who died of COVID-19, and found similar A\u03b2 deposits in all, using two different A\u03b2 antibodies across three different medical centers. The deposits failed to stain with Thioflavin-S. To investigate whether or not these deposits formed uniquely to COVID-19, we applied A\u03b2 immunostains to the autopsied brains of COVID-19-negative adults who died with acute respiratory distress syndrome and infants with severe cardiac anomalies, and also biopsy samples from patients with subacute cerebral infarcts. Cortical A\u03b2 deposits were also found in these cases, suggesting a link to hypoxia. The fate of these deposits and their effects on function are unknown, but it is possible that they contribute to the neurocognitive sequelae observed in some COVID-19 patients. Our findings may also have broader implications concerning hypoxia and its role in A\u03b2 deposition in the brain.<\/jats:p>","DOI":"10.1093\/jnen\/nlac095","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T18:15:46Z","timestamp":1666289746000},"page":"988-995","source":"Crossref","is-referenced-by-count":20,"title":["A\u03b2 Deposits in the Neocortex of Adult and Infant Hypoxic Brains, Including in Cases of COVID-19"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-5140","authenticated-orcid":false,"given":"David S","family":"Priemer","sequence":"first","affiliation":[{"name":"From the Department of Defense\/Uniformed Services University Brain Tissue Repository , Bethesda, Maryland, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. , Bethesda, Maryland, USA"},{"name":"Department of Pathology, Uniformed Services University, F. Edward H\u00e9bert School of Medicine , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Harker","family":"Rhodes","sequence":"additional","affiliation":[{"name":"From the Department of Defense\/Uniformed Services University Brain Tissue Repository , Bethesda, Maryland, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esma","family":"Karlovich","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai , New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P","family":"Perl","sequence":"additional","affiliation":[{"name":"From the Department of Defense\/Uniformed Services University Brain Tissue Repository , Bethesda, Maryland, USA"},{"name":"Department of Pathology, Uniformed Services University, F. Edward H\u00e9bert School of Medicine , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Goldman","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, The Taub Center for Research in Alzheimer\u2019s Disease and Aging, and the New York Presbyterian Hospital , New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"2024032523484493200_nlac095-B1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/s40478-020-01091-5","article-title":"Label-free vibrational imaging of different A\u03b2 plaque types in Alzheimer\u2019s disease reveals sequential events in plaque development","volume":"8","author":"R\u00f6hr","year":"2020","journal-title":"Acta Neuropathol Commun"},{"key":"2024032523484493200_nlac095-B2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrm2101","article-title":"Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer\u2019s amyloid beta-peptide","volume":"8","author":"Haass","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024032523484493200_nlac095-B3","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","article-title":"Phases of A beta-deposition in the human brain and its relevance for the development of AD","volume":"58","author":"Thal","year":"2002","journal-title":"Neurology"},{"key":"2024032523484493200_nlac095-B4","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/acn3.51350","article-title":"Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 \u201clong haulers\u201d","volume":"8","author":"Graham","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"key":"2024032523484493200_nlac095-B5","doi-asserted-by":"crossref","first-page":"101044","DOI":"10.1016\/j.eclinm.2021.101044","article-title":"Cognitive deficits in people who have recovered from COVID-19","volume":"39","author":"Hampshire","year":"2021","journal-title":"EClinicalMedicine"},{"key":"2024032523484493200_nlac095-B6","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1212\/CPJ.0000000000000897","article-title":"Potential neurologic manifestations of COVID-19","volume":"11","author":"Nordvig","year":"2021","journal-title":"Neurol Clin Pract"},{"key":"2024032523484493200_nlac095-B7","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-month neurological and psychiatric outcomes in 236\u2009379 survivors of COVID-19: A retrospective cohort study using electronic health records","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"2024032523484493200_nlac095-B8","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41591-021-01283-z","article-title":"Post-acute COVID-19 syndrome","volume":"27","author":"Nalbandian","year":"2021","journal-title":"Nat Med"},{"key":"2024032523484493200_nlac095-B9","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1093\/brain\/awab148","article-title":"COVID-19 neuropathology at Columbia University Irving Medical Center\/New York Presbyterian Hospital","volume":"144","author":"Thakur","year":"2021","journal-title":"Brain"},{"key":"2024032523484493200_nlac095-B10","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years","volume":"70","author":"Braak","year":"2011","journal-title":"J Neuropathol Exp Neurol"},{"key":"2024032523484493200_nlac095-B11","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 Pathol"},{"key":"2024032523484493200_nlac095-B12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00401-018-1862-7","article-title":"Convective influx\/glymphatic system: Tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways","volume":"136","author":"Albargothy","year":"2018","journal-title":"Acta Neuropathol"},{"key":"2024032523484493200_nlac095-B13","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.1523\/JNEUROSCI.0619-21.2021","article-title":"The glymphatic system: A novel component of fundamental neurobiology","volume":"41","author":"Hablitz","year":"2021","journal-title":"J Neurosci"},{"key":"2024032523484493200_nlac095-B14","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/BF00294806","article-title":"Ischemic stress induces deposition of amyloid beta immunoreactivity in human brain","volume":"90","author":"Jendroska","year":"1995","journal-title":"Acta Neuropathol"},{"key":"2024032523484493200_nlac095-B15","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/jnc.13932","article-title":"Hypoxia\/ischemia activate processing of amyloid precursor protein: Impact of vascular dysfunction in the pathogenesis of Alzheimer\u2019s disease","volume":"140","author":"Salminen","year":"2017","journal-title":"J Neurochem"},{"key":"2024032523484493200_nlac095-B16","doi-asserted-by":"crossref","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":"2024032523484493200_nlac095-B17","doi-asserted-by":"crossref","first-page":"10873","DOI":"10.1074\/jbc.M608856200","article-title":"Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation","volume":"282","author":"Zhang","year":"2007","journal-title":"J Biol Chem"},{"key":"2024032523484493200_nlac095-B18","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3389\/fnins.2015.00426","article-title":"Hypoxia affects neprilysin expression through caspase activation and an APP intracellular domain-dependent mechanism","volume":"9","author":"Kerridge","year":"2015","journal-title":"Front Neurosci"},{"key":"2024032523484493200_nlac095-B19","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The glymphatic pathway in neurological disorders","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol"},{"key":"2024032523484493200_nlac095-B20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1167\/iovs.61.13.24","article-title":"In vivo evidence for impaired glymphatic function in the visual pathway of patients with normal pressure hydrocephalus","volume":"61","author":"Jacobsen","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024032523484493200_nlac095-B21","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1161\/STROKEAHA.114.006617","article-title":"Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: A new target for fibrinolysis?","volume":"45","author":"Gaberel","year":"2014","journal-title":"Stroke"},{"key":"2024032523484493200_nlac095-B22","doi-asserted-by":"crossref","first-page":"104","DOI":"10.5607\/en.2019.28.1.104","article-title":"Persistent malfunction of glymphatic and meningeal lymphatic drainage in a mouse model of subarachnoid hemorrhage","volume":"28","author":"Pu","year":"2019","journal-title":"Exp Neurobiol"},{"key":"2024032523484493200_nlac095-B23","doi-asserted-by":"crossref","first-page":"860255","DOI":"10.3389\/fneur.2022.860255","article-title":"Impaired glymphatic transport kinetics following induced acute ischemic brain edema in a mouse pMCAO model [published correction appears in Front Neurol. 2022;13:929798]","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Neurol"},{"key":"2024032523484493200_nlac095-B24","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S2215-0366(20)30462-4","article-title":"Bidirectional associations between COVID-19 and psychiatric disorder: Retrospective cohort studies of 62\u2008354 COVID-19 cases in the USA [published correction appears in Lancet Psychiatry 2021 Jan;8(1):e1]","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"2024032523484493200_nlac095-B25","doi-asserted-by":"crossref","first-page":"117486","DOI":"10.1016\/j.jns.2021.117486","article-title":"A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications","volume":"426","author":"Frontera","year":"2021","journal-title":"J Neurol Sci"},{"key":"2024032523484493200_nlac095-B26","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/s13054-019-2626-z","article-title":"Long-term cognitive impairment after acute respiratory distress syndrome: A review of clinical impact and pathophysiological mechanisms","volume":"23","author":"Sasannejad","year":"2019","journal-title":"Crit Care"},{"key":"2024032523484493200_nlac095-B27","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1001\/jamapsychiatry.2022.1067","article-title":"Neuropsychiatric ramifications of severe COVID-19 and other severe acute respiratory infections","volume":"79","author":"Clift","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"2024032523484493200_nlac095-B28","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/jnen\/nlac030","article-title":"A history of senile plaques: From Alzheimer to amyloid imaging","volume":"81","author":"Beach","year":"2022","journal-title":"J Neuropathol Exp Neurol"}],"container-title":["Journal of Neuropathology &amp; Experimental Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/81\/12\/988\/47089348\/nlac095.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/81\/12\/988\/47089348\/nlac095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:33:01Z","timestamp":1711413181000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnen\/article\/81\/12\/988\/6764662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":28,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,10,20]]},"published-print":{"date-parts":[[2022,11,16]]}},"URL":"https:\/\/doi.org\/10.1093\/jnen\/nlac095","relation":{},"ISSN":["0022-3069","1554-6578"],"issn-type":[{"value":"0022-3069","type":"print"},{"value":"1554-6578","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,12,1]]},"published":{"date-parts":[[2022,10,20]]}}}