Abstract
The Notch signaling pathway is an evolutionarily conserved cell signaling system known to be involved in vascular development and function. Recent evidence suggests that dysfunctional Notch signaling could play a critical role in the pathophysiology of neurodegenerative diseases. We reviewed current literature on the role of Notch signaling pathway, and specifically Notch receptor genes and proteins, in aging, cerebrovascular disease and Alzheimer's disease. We hypothesize that Notch signaling may represent a key point of overlap between age-related vascular and Alzheimer's pathophysiology contributing to their comorbidity and combined influence on cognitive decline and dementia. Numerous findings from studies of genetics, neuropathology and cell culture models all suggest a link between altered Notch signaling and Alzheimer's pathophysiology. Age-related changes in Notch signaling may also trigger neurovascular dysfunction, contributing to the development of neurodegenerative diseases; however, additional studies are warranted. Future research directly exploring the influence of aberrant Notch signaling in the development of Alzheimer's disease is needed to better understand this mechanism.