Chronic cerebral hypoperfusion exacerbates amyloid and tau pathology by impairing glymphatic transport via AQP4- and VEGF-mediated pathways: insights from a vascular to mixed-type dementia model.

INTRODUCTION: Chronic cerebral hypoperfusion (CCH) is a major contributor to cognitive impairment; however, its underlying mechanisms remain poorly understood. METHODS: We investigated CCH-induced glymphatic dysfunction and neurodegeneration in amyloid precursor protein (APP)/presenilin 1 (PS1) and wild-type mice. Glymphatic transport was assessed using contrast-enhanced magnetic resonance imaging (MRI) and real-time femoral vein imaging. Aquaporin-4 (AQP4) polarization and amyloid beta (Aβ)/pho...