Klotho in Alzheimer's Disease: Evaluating Therapeutic Potential and Addressing Experimental Challenges

Alzheimer's Disease (AD), the most common neurodegenerative disorder, is characterized by cognitive decline and neurodegeneration. This review explores the intersection of AD pathology and Klotho, a protein linked to aging and cognitive enhancement. Klotho modulates aging-related processes, including amyloid-beta dynamics and neuroinflammation, through mechanisms such as autophagy enhancement, oxidative stress reduction, and amyloid-beta clearance. Research has indicated Klotho's potential in mitigating AD symptoms in murine models, such as APP/PS1. However, methodological challenges, including variability in experimental models and inconsistencies in Klotho administration, complicate the translation of these findings. This review synthesizes current research, highlights experimental limitations, and proposes methodological improvements to enhance the reliability and applicability of Klotho as a therapeutic target for AD, providing a foundation for future investigations that could revolutionize neurodegenerative disease management.