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Three-dimensional (3D) organoid and microfluidic technologies provide more physiologically relevant platforms for studying AD-associated neurovascular dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a membrane-free microfluidic endothelial barrier model integrated with neurospheroids derived from familial AD (FAD) neural progenitor cells. Human endothelial cells were cultured within perfusable microfluidic channels to establish a vascular-like interface rather than a fully specialized BBB endothelium. Pre-differentiated neurospheroids were grafted into the brain chamber. Endothelial barrier integrity, tight-junction expression, phosphorylated tau (pTau), and A\u03b242\/A\u03b240 production and distribution between compartments were assessed using immunofluorescence imaging and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The neurospheroid-grafted endothelial barrier construct captured key AD-associated phenotypes. ReN-AD-D4 models exhibited increased endothelial barrier permeability, reduced ZO-1 expression, and elevated pTau relative to controls. The platform supported endogenous A\u03b2 generation, accumulation, and endothelial-associated deposition at the endothelial barrier. ELISA demonstrated differential A\u03b242 and A\u03b240 distribution, consistent with isoform-selective behavior reported in AD pathology. Collectively, these results indicate co-occurring neuronal and endothelial barrier alterations within the integrated 3D system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This microfluidic endothelial barrier\u2013neurospheroid platform enables quantitative assessment of amyloid-\u03b2 accumulation, spatial distribution, and compartmentalized secretion alongside tau pathology and endothelial barrier integrity changes. Integrating human endothelial monolayers with FAD-derived neurospheroids, the system is scalable and compatible with high-content imaging. Although it does not model BBB-specific transport mechanisms, it provides a robust framework for hypothesis-driven studies of neurovascular interactions and therapeutic screening applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13041-026-01285-3","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T10:56:43Z","timestamp":1772535403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Recapitulating Alzheimer\u2019s disease pathophysiology with a microfluidic neurospheroid-grafted endothelial barrier model"],"prefix":"10.1186","volume":"19","author":[{"given":"Samuel Chidiebere","family":"Uzoechi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity","family":"Johnson-Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody Joseph","family":"Badeaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Su","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doo Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeoheung","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"1285_CR1","doi-asserted-by":"publisher","first-page":"937486","DOI":"10.3389\/fnagi.2022.937486","volume":"14","author":"X Li","year":"2022","unstructured":"Li X, Feng X, Sun X, Hou N, Han F, Liu Y. 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