Transcription factor EB improves Alzheimer’s disease via the autophagy-lysosome pathway

• Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway, and its activation enhances clearance of amyloid-β and Tau, mitigating neurotoxicity in Alzheimer’s disease. • Dysfunction of the autophagy-lysosome pathway contributes to the accumulation of neurotoxic protein aggregates, a hallmark of Alzheimer’s disease pathology. • Both pharmacological and non-pharmacological strategies that activate TFEB show promise in reducing amyloid-β deposition and Tau phosphorylation, improving cognitive outcomes in preclinical models. • Challenges remain, including potential risks of sustained TFEB activation (e.g., lysosomal storage disorders) and the need for targeted delivery systems to the brain for effective translation.