Short-term administration of iso-α-acids increases transthyretin transcription in the hippocampus

Cognitive decline and dementia are currently recognized as major problems in the aging population; however, there is still no promising treatment for these conditions. Previously, our group reported that iso-α-acids (IAAs), which are hop-derived bitter components present in beer, prevent inflammation and cognitive impairment in an Alzheimer's disease model mice (5xFAD mice) and yield significant reduction in amyloid β (Αβ) in the brain. However, data on the molecular mechanisms underlying these physiological effects of IAAs remain limited. Here, we used transcriptome analysis and found that oral administration of IAAs to 5xFAD mice for 7 days induces a 58.9-fold increase in the expression of transthyretin (TTR; Ttr) in the hippocampus compared with controls. In addition, real-time quantitative PCR showed that oral administration of IAAs significantly increased Ttr transcription in the hippocampi of wild type C57BL/6J mice but not in the cerebral cortex. TTR is an Αβ protein scavenger; thus, an increase in its expression could prevent amyloid aggregate formation. These results indicate that IAAs reduce Αβ in the brain by elevating TTR levels.