Adaptive Immune Dyshomeostasis as a Mediator of Vascular Cognitive Decline: Unraveling Neurovascular Crosstalk

作者：Yating Li, Jianlin Shen, Li Zhang, Yang Luo · 发表于：Aging and Disease · 年份：2025 · DOI：10.14336/ad.2025.0380 · 被引用次数：3 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Atherosclerosis and Cardiovascular Diseases、Neurological Disorders and Treatments

Vascular cognitive impairment and dementia (VCID), the second most prevalent form of dementia worldwide, arises from cerebrovascular injury and is increasingly recognized as an immune-mediated neurovascular disorder. Mounting evidence implicates dysregulated immune responses-both central and peripheral-as critical drivers of VCID pathogenesis. This review highlights the pivotal roles of microglial activation, astrocytic reactivity, and infiltration of pro-inflammatory T and B cells in disrupting the neurovascular unit (NVU). These processes, mediated by cytokines such as IL-6, IL-17A, and IFN-γ, contribute to the blood-brain barrier (BBB) breakdown, white matter degeneration, and neuronal dysfunction. We further examine how systemic inflammation and comorbidities including hypertension, diabetes, and gut dysbiosis exacerbate immune-neurovascular crosstalk. In light of these insights, we discuss emerging therapeutic strategies aimed at modulating neuroimmune interactions and restoring neurovascular integrity. This integrated perspective provides a foundation for developing precise, immune-targeted interventions in the prevention and treatment of VCID.