Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Department of Neuroscience, University of Virginia Center for Brain Immunology and Glia School of Medicine, Charlottesville, Virginia, USA.
Microcirculation. 2024 Oct;31(7):e12877. doi: 10.1111/micc.12877. Epub 2024 Sep 2.
The brain microvasculature, which delivers oxygen and nutrients and forms a critical barrier protecting the central nervous system via capillaries, is deleteriously affected by both Alzheimer's disease (AD) and type 2 diabetes (T2D). T2D patients have an increased risk of developing AD, suggesting potentially related microvascular pathological mechanisms. Pericytes are an ideal cell type to study for functional links between AD and T2D. These specialized capillary-enwrapping cells regulate capillary density, lumen diameter, and blood flow. Pericytes also maintain endothelial tight junctions to ensure blood-brain barrier integrity, modulation of immune cell extravasation, and clearance of toxins. Changes in these phenomena have been observed in both AD and T2D, implicating "pericyte pathology" as a common feature of AD and T2D. This review examines the mechanisms of AD and T2D from the perspective of the brain microvasculature, highlighting how pericyte pathology contributes to both diseases. Our review identifies voids in understanding how AD and T2D negatively impact the brain microvasculature and suggests future studies to examine the intersections of these diseases.
脑微血管通过毛细血管为中枢神经系统输送氧气和营养物质，并形成一个关键的屏障，但其同时受到阿尔茨海默病（AD）和 2 型糖尿病（T2D）的有害影响。T2D 患者患 AD 的风险增加，这表明存在潜在的相关微血管病理机制。周细胞是研究 AD 和 T2D 之间功能联系的理想细胞类型。这些专门的毛细血管包裹细胞调节毛细血管密度、管腔直径和血流。周细胞还维持内皮细胞紧密连接，以确保血脑屏障的完整性、调节免疫细胞渗出和清除毒素。在 AD 和 T2D 中都观察到了这些现象的变化，这表明“周细胞病理”是 AD 和 T2D 的共同特征。这篇综述从脑微血管的角度探讨了 AD 和 T2D 的发病机制，强调了周细胞病理如何导致这两种疾病。我们的综述确定了在理解 AD 和 T2D 如何对脑微血管产生负面影响方面存在的空白，并提出了未来研究这些疾病交叉点的建议。
