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Updated: May 26, 2026

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices
Published on: April 11, 2018
Neurovascular unit failure as the opening chapter of dementia pathogenesis
1Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.
Abstract:
Neurovascular dysfunction is increasingly recognized as a central feature of dementia pathogenesis in the early or even preclinical stage, rather than merely a downstream effect of amyloid-tau neurodegeneration. Based on multimodal clinical evidence showing that cerebrovascular dysregulation can precede amyloid-β accumulation, this commentary emphasizes three converging lines: (1) hippocampal blood-brain barrier breakdown as an early, potentially amyloid-/tau-independent event, (2) vascular-first/parallel two-hit frameworks linking vascular risk factors to subsequent proteinopathy, and (3) early neurovascular coupling failure and chronic hypoperfusion as upstream drivers. Integrating blood-brain barrier and hemodynamic biomarkers may facilitate earlier biological subtyping and prevention.
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