Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease

Alzheimer's disease (AD), which is an irreversible neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles, is the most common form of dementia worldwide. However, currently, there are no satisfying curative therapies for AD. The blood-brain barrier (BBB) acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. BBB dysfunction as an upstream or downstream event promotes the onset and progression of AD. Moreover, the pathogenesis of AD caused by BBB injury hasn't been well elucidated. Glial cells, BBB compartments and neurons form a minimal functional unit called the neurovascular unit (NVU). Emerging evidence suggests that glial cells are regulators in maintaining the BBB integrity and neuronal function. Illustrating the regulatory mechanism of glial cells in the BBB assists us in drawing a glial-vascular coupling diagram of AD, which may offer new insight into the pathogenesis of AD and early intervention strategies for AD. This review aims to summarize our current knowledge of glial-BBB interactions and their pathological implications in AD and to provide new therapeutic potentials for future investigations.