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Glymphatic transport was assessed using contrast\u2010enhanced magnetic resonance imaging (MRI) and real\u2010time femoral vein imaging. Aquaporin\u20104 (AQP4) polarization and amyloid beta (A\u03b2)\/phosphorylated tau 217 (p\u2010tau217) accumulation were examined by immunofluorescence staining. Single\u2010cell RNA sequencing (scRNA\u2010seq) identified molecular mechanisms and pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>CCH impaired glymphatic clearance by reducing AQP4 polarization, resulting in A\u03b2 and p\u2010tau217 accumulation. scRNA\u2010seq revealed downregulation of vascular endothelial growth factor (VEGF), Rho GTPase, and integrin\u2013actin signaling pathways. Restoring vascular tone with adrenergic receptor blocker normalized VEGF localization and vascular pulsatility\/resistance, improved glymphatic clearance, and rescued cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>CCH impairs glymphatic function through AQP4 depolarization and VEGF suppression, causing toxic protein accumulation. Restoring vascular tone rescued cognition, establishing a mechanistic link between vascular dysfunction and neurodegeneration in cognitive impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71290","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:40:29Z","timestamp":1773747629000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Chronic cerebral hypoperfusion exacerbates amyloid and tau pathology by impairing glymphatic transport via AQP4\u2010 and VEGF\u2010mediated pathways: insights from a vascular to mixed\u2010type dementia model"],"prefix":"10.1002","volume":"22","author":[{"given":"Jia\u2010Hung","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology Taipei Medical University\u2010Shuang Ho Hospital  New Taipei Taiwan"},{"name":"Department of Neurology School of Medicine College of Medicine Taipei Medical University  Taipei Taiwan"},{"name":"Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Wen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You\u2010Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"},{"name":"Department of Biomedical Engineering National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine College of Medicine Taipei Medical University  Taipei Taiwan"},{"name":"Research Center for Neuroscience Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Bin","family":"Yang","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"},{"name":"Research Center for Neuroscience Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao\u2010Wen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Yang Ming Chiao Tung University  Taipei 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