{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:47:08Z","timestamp":1793141228066,"version":"4.5.0"},"reference-count":82,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"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":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein E\u03b54 (APOE\u03b54) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>PET imaging was used to assess metabolism\u2010perfusion in both sexes of aging C57BL\/6J, and hAPOE mice, and were verified by transcriptomics, and immunopathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>All hAPOE strains showed AD phenotype progression by 8\u00a0months, with females exhibiting the regional changes, which correlated with GO\u2010term enrichments for glucose metabolism, perfusion, and immunity. Uncoupling analysis revealed APOE\u03b54\/\u03b54 exhibited significant Type\u20101 uncoupling (\u2193 glucose uptake, \u2191 perfusion) at 8 and 12\u00a0months, while APOE\u03b53\/\u03b54 demonstrated Type\u20102 uncoupling (\u2191 glucose uptake, \u2193 perfusion), while immunopathology confirmed cell specific contributions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This work highlights APOE\u03b54 status in AD progression manifests as neurovascular uncoupling driven by immunological activation, and may serve as an early diagnostic biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            We developed a novel analytical method to analyze PET imaging of\n                            <jats:sup>18<\/jats:sup>\n                            F\u2010FDG and\n                            <jats:sup>64<\/jats:sup>\n                            Cu\u2010PTSM data in both sexes of aging C57BL\/6J, and hAPOE\u03b53\/\u03b53, hAPOE\u03b54\/\u03b54, and hAPOE\u03b53\/\u03b54 mice to assess metabolism\u2010perfusion profiles termed neurovascular uncoupling.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This analysis revealed APOE\u03b54\/\u03b54 exhibited significant Type\u20101 uncoupling (decreased glucose uptake, increased perfusion) at 8 and 12 months, while APOE\u03b53\/\u03b54 demonstrated significant Type\u20102 uncoupling (increased glucose uptake, decreased perfusion) by 8 months which aligns with immunopathology and transcriptomic signatures.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This work highlights that there may be different mechanisms underlying age related changes in APOE\u03b54\/\u03b54 compared with APOE\u03b53\/\u03b54. We predict that these changes may be driven by immunological activation and response, and may serve as an early diagnostic biomarker.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13842","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T13:29:48Z","timestamp":1715088588000},"page":"4951-4969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Assessment of neurovascular uncoupling:\n                    <i>APOE<\/i>\n                    status is a key driver of early metabolic and vascular dysfunction"],"prefix":"10.1002","volume":"20","author":[{"given":"Kristen D.","family":"Onos","sequence":"first","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter 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