DIURNAL GUT BRAIN COMMUNICATION IN ALZHEIMER'S DISEASE

Alzheimer’s disease (AD) is a devastating neurodegenerative process. Altered circadian clock-controlled behavioural processes such as a disturbed sleep–wake cycle, as well as functional deterioration in the Suprachiasmatic nucleus (SCN), home of the central clock, have been associated with AD. Decline of central clock function in the SCN of AD patients and alterations in the signalling pathways downstream of the SCN likely result in a weakening of systemic circadian clock network integrity. AD is increasingly perceived to not only affect the brain, but also to impact on peripheral tissue physiology. In turn, peripheral tissues can modulate the pathology in the brain. This is particularly true for the intestine and its role in the microbiota – gut – brain axis. AD patients develop dysbiosis at early stages of the disease and transplantation of AD-related microbiota propagates AD-like symptoms to healthy recipients, suggesting that the microbiota contributes to the development of AD pathology. Importantly, abundance, location and composition of the intestinal microbiota follows a diurnal rhythm, which is regulated by and feeds back into the host circadian clock network. Whether deteriorating circadian rhythmicity in the microbiota – gut – brain axis contributes to AD development is not known. Following a multi-omic approach, combining metagenomic, metabolomic, and transcriptomic analyses, we present how AD-related pathology is altering circadian rhythmicity along the microbiota-gut-brain axis in a sex-specific manner in mice. The implications of altered circadian rhythmicity along the microbiota-gut-brain axis on disease progression will be discussed.