Reduction of Alzheimers disease beta-amyloid pathology in the absence of gut microbiota

Alzheimers disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimers disease is not known. We generated a germ-free mouse model of Alzheimers disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimers disease animals with intestinal microbiota. Sequencing bacterial 16S rRNA from fecal samples revealed a remarkable shift in the gut microbiota of conventionally-raised Alzheimers disease mice as compared to healthy, wild-type mice. Colonization of germ-free Alzheimer mice with harvested microbiota from conventionally-raised Alzheimer mice dramatically increased cerebral Ab pathology. In contrast, colonization with microbiota from control wild-type mice was ineffective in increasing cerebral Ab levels. Our results indicate a microbial involvement in the development of Alzheimers disease pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.