{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:54:36Z","timestamp":1791665676717,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent advances in anti-amyloid therapies for Alzheimer\u2019s disease have been promising, but they have also highlighted critical challenges, including increased vascular complications, such as amyloid-related imaging abnormalities. Emerging evidence suggests that the soluble epoxide hydrolase may be a promising therapeutic target due to the involvement of sEH-derived diols in inflammation, oxidative stress, and vascular destabilization.<\/jats:p>\n                  <jats:p>APPPS1 mice, a model of amyloidosis, were crossed with an inducible soluble epoxide hydrolase knock-out mouse line. The knock-out was induced before onset of amyloid deposition, and then the mice were analyzed using histological, molecular, and RNA sequencing techniques.<\/jats:p>\n                  <jats:p>Here, we identify astrocytic soluble epoxide hydrolase as a key mediator of vascular instability in amyloid pathology. Targeted astrocyte-specific deletion of soluble epoxide hydrolase in APPPS1 mice dramatically mitigated vascular changes, reducing the vascular amyloid burden by 67.95% and preserving VE-cadherin architecture. Importantly, vasomotion was markedly impaired in the Alzheimer\u2019s disease model and was preserved in soluble epoxide hydrolase-deficient animals. Transcriptomic profiling of vasculature in APPPS1xsEH\u0394AC mice revealed upregulated expression of genes critical for neurovascular protection.<\/jats:p>\n                  <jats:p>These findings identify soluble epoxide hydrolase as a central regulator of neurovascular dysfunction and underscore its therapeutic potential in increasing vascular stability in amyloidosis-associated diseases, such as Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awag184","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:43:40Z","timestamp":1779363820000},"source":"Crossref","is-referenced-by-count":1,"title":["Soluble epoxide hydrolase drives neurovascular dysfunction in a model of amyloidosis"],"prefix":"10.1093","author":[{"given":"Murphy","family":"DeMeglio","sequence":"first","affiliation":[{"name":"Neurovascular Disorders, Institute of Cell Biology and Neuroscience, Biologicum, Goethe University Frankfurt , 60438 Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloah S","family":"De Biasi","sequence":"additional","affiliation":[{"name":"Neurovascular Disorders, Institute of Cell Biology and Neuroscience, Biologicum, Goethe University Frankfurt , 60438 Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Breunig","sequence":"additional","affiliation":[{"name":"Neurovascular Disorders, Institute of Cell Biology and Neuroscience, Biologicum, Goethe University Frankfurt , 60438 Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-3024","authenticated-orcid":false,"given":"Michael","family":"Candlish","sequence":"additional","affiliation":[{"name":"Neurovascular Disorders, Institute of Cell Biology and Neuroscience, Biologicum, Goethe University Frankfurt , 60438 Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Sauerland","sequence":"additional","affiliation":[{"name":"Neurovascular Disorders, Institute of Cell Biology and Neuroscience, Biologicum, Goethe University Frankfurt , 60438 Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research , Bad Nauheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruya","family":"Kawase","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research , Bad Nauheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Peguera","sequence":"additional","affiliation":[{"name":"Buchmann Institute for Molecular Life Sciences (BMLS), Institute of Cell Biology and Neuroscience, Goethe University Frankfurt , 60438, Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bohnstaedt","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Brain Research , 60438, Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilians University of Munich , 81377, Munich ,","place":["Germany"]},{"name":"Neuroimmunology and Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) , 81377, Munich ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Neubauer","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilians University of Munich , 81377, Munich ,","place":["Germany"]},{"name":"Neuroimmunology and Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) , 81377, Munich ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas J","family":"Neher","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) , 81377, Munich ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich ,","place":["Germany"]},{"name":"Biomedical Center (BMC), Biochemistry, Faculty of Medicine , LMU Munich, 82152, Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry and Biology, Link\u00f6ping University , SE-581 83, Link\u00f6ping ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute for Vascular Signaling, Centre for Molecular Medicine, Goethe University Frankfurt , 60596, Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-4636","authenticated-orcid":false,"given":"Susanne","family":"Hille","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine V with a focus on angiology, Campus Kiel; Universit\u00e4tsklinikums Schleswig-Holstein 24105 , Kiel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine V with a focus on angiology, Campus Kiel; Universit\u00e4tsklinikums Schleswig-Holstein 24105 , Kiel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Acker-Palmer","sequence":"additional","affiliation":[{"name":"Buchmann Institute for Molecular Life Sciences (BMLS), Institute of Cell Biology and Neuroscience, Goethe University Frankfurt , 60438, Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D","family":"Hammock","sequence":"additional","affiliation":[{"name":"Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California , Davis, California 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Michael","family":"Underhill","sequence":"additional","affiliation":[{"name":"University of British Columbia, Dept. of Cellular and Physiological Sciences, and School of Biomedical Engineering , V6T 1Z3, Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Junek","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Brain Research , 60438, Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research , Bad Nauheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Fleming","sequence":"additional","affiliation":[{"name":"Institute for Vascular Signaling, Centre for Molecular Medicine, Goethe University Frankfurt , 60596, Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8994-2536","authenticated-orcid":false,"given":"Jasmin K","family":"Hefendehl","sequence":"additional","affiliation":[{"name":"Neurovascular Disorders, Institute of Cell Biology and Neuroscience, Biologicum, Goethe University Frankfurt , 60438 Frankfurt am Main ,","place":["Germany"]},{"name":"Buchmann Institute for Molecular Life Sciences (BMLS), Institute of Cell Biology and Neuroscience, Goethe University Frankfurt , 60438, Frankfurt am Main 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