{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:17:16Z","timestamp":1777396636010,"version":"3.51.4"},"reference-count":74,"publisher":"SAGE Publications","issue":"s2","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"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":[[2024,5,7]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) is associated with impaired cerebral circulation which underscores diminished delivery of blood oxygen and nutrients to and throughout the brain. In the 3xTg-AD mouse model, we have recently found that\u200a&gt;\u200a10 cerebrovascular miRNAs pertaining to vascular permeability, angiogenesis, and inflammation (e.g., let-7d, miR-99a, miR-132, miR-133a, miR-151-5p, and miR-181a) track early development of AD. Further, endothelial-specific miRNAs (miR-126-3p, miR-23a\/b, miR-27a) alter with onset of overall AD pathology relative to stability of smooth muscle\/pericyte-specific miRNAs (miR-143, miR-145).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We tested the hypothesis that cerebrovascular miRNAs indicating AD pathology share mRNA targets that regulate key endothelial cell functions such as angiogenesis, vascular permeability, and blood flow regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>As detected by NanoString nCounter miRNA Expression panel for 3xTg-AD mice, 61 cerebrovascular miRNAs and respective mRNA targets were examined using Ingenuity Pathway Analysis for canonical Cardiovascular (Cardio) and Nervous System (Neuro) Signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The number of targets regulated per miRNA were 21\u00b12 and 33\u00b13 for the Cardio and Neuro pathways respectively, whereby 14\u00b12 targets overlap among pathways. Endothelial miRNAs primarily target members of the PDE, PDGF, SMAD, and VEGF families. Individual candidates regulated by\u22654 miRNAs that best mark AD pathology presence in 3xTg-AD mice include CFL2, GRIN2B, PDGFB, SLC6A1, SMAD3, SYT3, and TNFRSF11B.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>miRNAs selective for regulation of endothelial function and respective downstream mRNA targets support a molecular basis for dysregulated cerebral blood flow regulation coupled with enhanced cell growth, proliferation, and inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230300","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T11:42:30Z","timestamp":1689334950000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Cerebrovascular miRNAs Track Early Development of Alzheimer\u2019s Disease and Target Molecular Markers of Angiogenesis and Blood Flow Regulation"],"prefix":"10.1177","volume":"99","author":[{"given":"Phoebe P.","family":"Chum","sequence":"first","affiliation":[{"name":"Basic Sciences, Loma Linda University, Loma Linda, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary A.","family":"Bishara","sequence":"additional","affiliation":[{"name":"Basic Sciences, Loma Linda University, Loma Linda, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Summer R.","family":"Solis","sequence":"additional","affiliation":[{"name":"Basic Sciences, Loma Linda University, Loma Linda, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik J.","family":"Behringer","sequence":"additional","affiliation":[{"name":"Basic Sciences, Loma Linda University, Loma Linda, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,5]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac174"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.12.018"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa132"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.05.004"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.3919"},{"key":"e_1_3_6_8_2","doi-asserted-by":"crossref","first-page":"e12295","DOI":"10.1002\/trc2.12295","article-title":"Alzheimer\u2019s disease drug development pipeline: 2022","volume":"8","author":"Cummings J","year":"2022","unstructured":"CummingsJ, LeeG, NahedP, KambarM, ZhongK, FonsecaJ, TaghvaK (2022) Alzheimer\u2019s disease drug development pipeline: 2022. 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