{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:23:21Z","timestamp":1777397001309,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a complex neurodegenerative disease marked by increased amyloid-\u03b2 (A\u03b2) deposition, tau hyperphosphorylation, impaired energy metabolism, and chronic ischemia-type injury. Cerebral microvascular dysfunction likely contributes to AD pathology, but its precise pathogenic role has been poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine microvascular reactivity to endothelium-dependent vasodilators and small conductance calcium-activated potassium (SK) channel activity in an intracerebral streptozotocin (STZ)-induced AD mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Control and STZ-AD mice underwent Morris Water Maze and Barnes testing, after which cerebral microvascular and brain microvascular endothelial cells (MBMECs) were dissected to assess microvascular reactivity, responses to SK channel activator NS309, and ion-channel current recordings using whole-cell patch clamp methodology. Control mouse cerebral microvascular and human brain microvascular endothelial cells (HBMECs) were treated with soluble A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      peptide to characterize microvascular reactivity and endothelial potassium currents.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>STZ-AD mice exhibited impaired performance vs control mice in behavioral testing. STZ-AD mice also exhibited diminished cerebral microvascular responsiveness and MBMECs potassium current augmentation in response to NS309 compared with control mice. Incubation of control mouse cerebral micro-vessels and HBMECs with soluble A\u03b2 (1\u2005\u00b5M) for 2\u2005h attenuated relaxation responses to NS309 and diminished NS309-sensitive endothelial potassium currents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>STZ-AD mice exhibited impaired microvascular relaxation responses to endothelium-dependent vasodilators; SK\/IK channel dysfunction may be involved in the mechanism of this impairment. Acute treatment with A\u03b2 produced dysregulated cerebrovascular endothelial SK\/IK channels. Further elucidation of the role of microvascular dysfunction in AD is needed to prevent the chronic ischemia-type injury that contributes to cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241309120","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T06:06:21Z","timestamp":1736489181000},"page":"1112-1125","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Impaired cerebral microvascular reactivity and endothelial SK channel activity in a streptozotocin-treated mouse model of Alzheimer's disease"],"prefix":"10.1177","volume":"103","author":[{"given":"Hang","family":"Xing","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4961-9691","authenticated-orcid":false,"given":"Shawn","family":"Kant","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghamsh","family":"Kanuparthy","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwight","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Stone","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Broadwin","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Pearson","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ava","family":"Sauer","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Princiotto","sequence":"additional","affiliation":[{"name":"Vascular Research Laboratory, Providence VA Medical Center, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth O","family":"Harrington","sequence":"additional","affiliation":[{"name":"Vascular Research Laboratory, Providence VA Medical Center, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne M","family":"de la Monte","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Sellke","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_3_5_2_2","unstructured":"Alzheimer's disease facts and figures. 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