Spreading of Tau and other corrupted proteins through the gut‐brain axis

Alzheimer’s disease (AD) is the most common form of dementia. However, although the clinical and pathological aspect of the disease are thoroughly characterized, the pathophysiological mechanism underlying the progressive neurodegenerative process is not well understood. In consequence, there is no cure and a disease‐modifying treatment is lacking. It is therefore imperative to identify the earliest signs of disease pathology to pave the way to identify the triggering molecular factors of the disease and the mechanisms underlying molecular spreading of toxic assemblies. Our search for these key clues in the periphery is founded on the fact that peripheral dysfunction, particularly in the gastrointestinal (GI) system, can arise decades before the onset of the classic symptoms in neurodegenerative disorders. In fact, the risk of AD increases significantly in patients with inflammatory bowel disease (IBD) when compared with the non‐IBD population. Furthermore, Tau accumulates in Crohn’s Disease guts and in sigmoid colon of AD and FTD patients. Therefore, we are investigating the physiological and molecular mechanisms that support Tau spreading in the prodromal stages and, particularly, along the gut‐brain axis.