Krüppel-like factor 4 transcription factor in blood–brain barrier endothelial cells: A potential role in Alzheimer's disease

Abstract

Alzheimer's disease is the most prevalent chronic neurodegenerative disorder worldwide, with no sufficient cure. Ongoing research is focused on developing new therapies aimed at preventing or delaying the onset of symptoms, slowing disease progression, and improving cognitive and behavioral outcomes in individuals affected by Alzheimer's disease. Among the various pathological changes associated with this condition, blood–brain barrier (BBB) leakage plays a crucial role as it serves as a vital boundary for maintaining central nervous system (CNS) health. Preserving the integrity and functionality of the BBB is essential to protect the brain from amyloid-β accumulation, neuroinflammation, and neuronal degeneration. This review summarizes models of Alzheimer's disease characterized by BBB leakage over time. More importantly, we introduce Krüppel-like factor 4 (KLF4), a transcription factor involved in vascular systems, and discuss its relevance to Alzheimer's disease. By elucidating the functions of KLF4 within both vascular and CNSs, this review highlights its potential role in modulating BBB integrity in Alzheimer's pathology, which may contribute to therapeutic strategies for managing this debilitating condition.