Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer's Disease.

ABSTRACT

Endothelial cells are constantly exposed to environmental stress factors that, above a certain threshold, trigger cellular senescence and apoptosis. The altered vascular function affects new vessel formation and endothelial fitness, contributing to the progression of age-related diseases. This narrative review highlights the complex interplay between senescence, oxidative stress, extracellular vesicles, and the extracellular matrix and emphasizes the crucial role of angiogenesis in aging and Alzheimer's disease. The interaction between the vascular and nervous systems is essential for the development of a healthy brain, especially since neurons are exceptionally dependent on nutrients carried by the blood. Therefore, anomalies in the delicate balance between pro- and antiangiogenic factors and the consequences of disrupted angiogenesis, such as misalignment, vascular leakage and disturbed blood flow, are responsible for neurodegeneration. The implications of altered non-productive angiogenesis in Alzheimer's disease due to dysregulated Delta-Notch and VEGF signaling are further explored. Additionally, potential therapeutic strategies such as exercise and caloric restriction to modulate angiogenesis and vascular aging and to mitigate the associated debilitating symptoms are discussed. Moreover, both the roles of extracellular vesicles in stress-induced senescence and as an early detection marker for Alzheimer's disease are considered. The intricate relationship between endothelial senescence and angiogenesis provides valuable insights into the mechanisms underlying angiogenesis-related disorders and opens avenues for future research and therapeutic interventions.