J Alzheimers Dis. 2025 Sep 12:13872877251377793. doi: 10.1177/13872877251377793. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder primarily affecting the aging population, characterized by progressive cognitive decline. Traditional models of AD pathogenesis, including the amyloid cascade and tau hypotheses, have not yielded definitive therapeutic breakthroughs. Emerging research suggests that metabolic dysfunction, particularly in glucose transport, plays a central role in AD progression. The glucose transporter 1 (GLUT1), which facilitates glucose entry across the blood-brain barrier, is crucial for maintaining brain energy metabolism. Studies have shown reduced GLUT1 expression in AD brains, impairing cerebral glucose uptake and contributing to neuronal dysfunction and neurodegeneration. This review synthesizes current evidence on the interplay between GLUT1 alteration and AD, highlighting how disruptions in glucose transport can exacerbate the disease’s neuropathological features, including amyloid and tau pathologies. Furthermore, we explore potential therapeutic strategies aimed at restoring GLUT1 function, such as gene therapy, ketogenic diets, and small molecules that enhance GLUT1 expression. These approaches may offer promising avenues to mitigate the metabolic dysfunction driving AD and improve patient outcomes. This work underscores the importance of integrating metabolic insights into AD research to develop innovative therapeutic targets and interventions.

PMID:40944317 | DOI:10.1177/13872877251377793

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