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Characterized by the presence of amyloid plaques, neurofibrillary tangles and neuroinflammation, Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no known treatment or cure. Global disease projections warrant an urgent and rapid therapeutic for the treatment of this devastating disease. Fecal microbiota transplantation (FMT) is a widely accepted and safely used treatment for recurrent Clostridium difficile infection and other metabolic diseases such as diabetes mellitus. FMT has also been demonstrated to be a possible AD therapeutic. We examined the potential of FMT for the treatment of AD in a robust, mouse model of the disease and report that a brief, 7-day treatment regimen demonstrated ‘plaque-busting’ and behavior-modifying effects in treated 5xFAD mice. Importantly, we show that donor age plays an important role in the efficacy of the treatment and these findings warrant further investigation in human trials.

The efficacy of fecal microbiota transplantation (FMT) in Alzheimer's disease has yet to be investigated. Here, we show that FMT is capable of providing neuroprotective effects in two groups of treated 5xFAD Alzheimer's mice, old transgenic (Tg) mice fed fecal slurry from healthy, wild-type donors of similar age (Old Tg-FO) and old mice fed fecal slurry from younger healthy, wild-type donors (Old Tg-FY). Improved spatial and recognition memory in Old Tg-FY and 15 enhanced recognition memory in Old Tg-FO were observed when compared to Old Tg-Control mice given saline. Crucially, there was significant decreases in cortical Ab loading in all treated mice, demonstrating the therapeutic effects of FMT in improving cognition and reducing amyloid pathology in AD brains.One Sentence Summary: Fecal microbial transplants reduce amyloid pathology and improve 20 cognition in Alzheimer's mice.

Background The efficacy of fecal microbiota transplantation (FMT) as a therapeutic in Alzheimer's disease was evaluated in the 5XFAD mouse model. Method We treated sixteen, 36‐week‐old 5XFAD transgenic mice with fecal slurry from healthy, wild‐type donors of similar age (n = 8; Old Tg‐FO) or from younger (8‐10‐week old) healthy, wild‐type donors (n = 8; Old Tg‐FY) for seven days. Mice were incubated for 21 days and were then subjected to cognitive tests to examine the effects of FMT on memory. Mice were sacrificed and brain tissue was examined for amyloid plaque load. Result Improved spatial and recognition memory in Old Tg‐FY and enhanced recognition memory in Old Tg‐FO mice were observed when compared to Old Tg‐Control mice treated with saline. Importantly, there were significant decreases in cortical Ab loading following seven days of FMT in all treated mice. Conclusion Our results demonstrate the capability FMT in improving cognition and reducing amyloid pathology in the 5XFAD mouse model of Alzheimer’s.