The gut microbiome in preclinical Alzheimer Disease

The current paradigm of Alzheimer Disease (AD) pathology builds on a progression from cognitively normal status, to cognitively normal with biomarker evidence of disease (preclinical AD), to symptomatic AD characterized by both abnormal biomarker levels and cognitive impairment. Recent work has demonstrated that the gut microbiomes of symptomatic AD patients have distinct taxonomic compositions compared to healthy cognitively normal controls. However, knowledge about changes in the gut microbiome prior to the onset of symptomatic AD is limited. In this cross-sectional study we compared the taxonomic composition, microbial functional potential, and abundances of metagenome-assembled genomes (MAGs) in a cohort of 43 cognitively normal individuals with preclinical AD and 50 cognitively normal individuals without evidence of AD. An observation of gut microbiome correlates of preclinical AD neuropathology has the potential to improve our understanding of AD etiology, enable the identification of gut-derived biomarkers of AD or AD risk, and inform the development of therapeutic interventions.