Micro and Nano 3D investigation of complex gut alterations-dementia interplay

Abstract

Alzheimer's disease (AD), a debilitating neurodegenerative disorder, remains one of the foremost public health challenges of our time. Despite decades of research, its etiology largely remains enigmatic. Recently, attention has turned to the gut-brain axis, a complex network of communication between the gastrointestinal tract and the brain, as a potential player in the pathogenesis of AD. Here we exploited X-ray Phase Contrast Tomography to provide an in-depth analysis of the link between the gut condition and AD, exploring gut anatomy and structure in murine models. We conducted a comprehensive analysis by comparing the outcomes in various mouse models of cognitive impairment, including AD, frail mice, and frontotemporal dementia (FTD) affected mice. We discovered an association between substantial changes in the gut structure and the presence of amyloid-beta (A\b{eta}) in the brain. We found that the most important gut alterations are related to A\b{eta} occurrence in the brain. In particular, we investigated the gut morphology, the distribution of enteric micro-processes and neurons in the ileum. Understanding the intricate interplay between gut condition and dementia may open new avenues for early AD diagnosis and treatment offering hope for a future where these diseases may be more effectively addressed.