Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

TLDR

Alzheimer’s disease is the most common dementia in the western world and currently has no cure, while the role of gut microbiota in its pathogenesis remains unknown. The study aimed to investigate gut microbiota differences in an APP transgenic mouse model by sequencing fecal 16S rRNA. Germ‑free APP transgenic mice were generated to assess the impact of microbiota on cerebral amyloid pathology. Compared to conventional mice, germ‑free APP mice showed a drastic reduction in cerebral Aβ amyloid, and recolonization with microbiota from APP mice increased pathology whereas microbiota from wild‑type mice had a lesser effect, indicating a microbial contribution to amyloid development.

Abstract

Abstract Alzheimer’s 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 Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.