{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:22:19Z","timestamp":1791912139239,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41 EB015909"],"award-info":[{"award-number":["P41 EB015909"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH084021"],"award-info":[{"award-number":["R01 MH084021"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1 AG071515"],"award-info":[{"award-number":["RF1 AG071515"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG064792"],"award-info":[{"award-number":["R01 AG064792"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS106711"],"award-info":[{"award-number":["R01 NS106711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS106702"],"award-info":[{"award-number":["R01 NS106702"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AG058413"],"award-info":[{"award-number":["R21 AG058413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>\n                    Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for \u201cunbiased descriptive classification\u201d, biomarkers of neurodegeneration, \u201cN\u201d, constitute a critical component in the tri\u2010category \u201cA\/T\/N\u201d system. Current biomarkers of neurodegeneration suffer from potential drawbacks such as requiring invasive lumbar puncture, involving ionizing radiation, or representing a late, irreversible marker. Recent human studies have suggested that reduced brain oxygen metabolism may be a new functional marker of neurodegeneration in AD, but the heterogeneity and the presence of mixed pathology in human patients did not allow a full understanding of the role of oxygen extraction and metabolism in AD. In this report, global brain oxygen metabolism and related physiological parameters were studied in two AD mouse models with relatively pure pathology, using advanced MRI techniques including T\n                    <jats:sub>2<\/jats:sub>\n                    \u2010relaxation\u2010under\u2010spin\u2010tagging (TRUST) and phase contrast (PC) MRI. Additionally, regional cerebral blood flow (CBF) was determined with pseudocontinuous arterial spin labeling. Reduced global oxygen extraction fraction (by \u221218.7%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008), unit\u2010mass cerebral metabolic rate of oxygen (CMRO\n                    <jats:sub>2<\/jats:sub>\n                    ) (by \u221217.4%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04) and total CMRO\n                    <jats:sub>2<\/jats:sub>\n                    (by \u221230.8%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) were observed in Tau4R\u0394K mice\u2014referred to as the tau AD model\u2014which manifested pronounced neurodegeneration, as measured by diminished brain volume (by \u221215.2%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Global and regional CBF in these mice were not different from those of wild\u2010type mice (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05), suggesting normal vascular function. By contrast, in B6;SJL\u2010Tg [APPSWE]2576Kha (APP) mice\u2014referred to as the amyloid AD model\u2014no brain volume reduction, as well as relatively intact brain oxygen extraction and metabolism, were found (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Consistent with the imaging data, behavioral measures of walking distance were impaired in Tau4R\u0394K mice (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004), but not in APP mice (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.88). Collectively, these findings support the hypothesis that noninvasive MRI measurement of brain oxygen metabolism may be a promising biomarker of neurodegeneration in AD.\n                  <\/jats:p>","DOI":"10.1002\/nbm.4568","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T06:18:57Z","timestamp":1622787537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Brain metabolism in tau and amyloid mouse models of Alzheimer's disease: An MRI study"],"prefix":"10.1002","volume":"34","author":[{"given":"Zhiliang","family":"Wei","sequence":"first","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Research Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9698-5622","authenticated-orcid":false,"given":"Jiadi","family":"Xu","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Research Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Research Institute  Baltimore Maryland USA"},{"name":"Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance Xiamen University  Xiamen Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydiane","family":"Hirschler","sequence":"additional","affiliation":[{"name":"Inserm, U1216, Grenoble Institut Neurosciences Universit\u00e9 Grenoble Alpes  Grenoble France"},{"name":"C. J. Gorter Center for High Field MRI, Department of Radiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4952-1240","authenticated-orcid":false,"given":"Emmanuel L.","family":"Barbier","sequence":"additional","affiliation":[{"name":"Inserm, U1216, Grenoble Institut Neurosciences Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-1564","authenticated-orcid":false,"given":"Hanzhang","family":"Lu","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. 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