Methylene blue decreases brain mitochondrial ABAD and amyloid beta levels protecting mitochondrial functions in LPS-mouse model

Abstract

Background Methylene blue (MB) is lately being proposed to be effective in treating Alzheimer’s disease (AD). Phase 2 clinical trials reported improvements in cognitive functions of AD patients after MB treatment. One of the main mechanisms of action that has been described for MB is inhibition of Tau aggregation [1]. Moreover, its antioxidant and mitochondrial protection have been previously described [2]. Only recently, a study using a triple transgenic AD mouse model has tested the mechanism of MB in vivo, showing improved cognition and reduced Ab levels after MB treatment [3]. Recently, the mitochondrial enzyme Amyloid binding alcohol dehydrogenase (ABAD) has been shown to bind Ab inducing mitochondrial dysfunction, providing a direct relation between Ab and mitochondrial dysfunction occurring in AD. Previous studies have shown that inhibiting ABAD protects mitochondrial functions and prevented Ab-induced toxicity [4][5]. Taking into consideration the mitochondrial protective effect of MB and the recent data suggesting its ability to reduce Ab levels, our aim was to investigate the effect of MB on ABAD and mitochondrial function in an LPS mouse model that has been previously described to induce memory impairment, with Ab accumulation in hippocampus and cerebral cortex [6].