How the gut microbiota impacts neurodegenerative diseases by modulating CNS immune cells

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Amyloid-β (Aβ) accumulation and neurofibrillary tangles are two key histological features resulting in progressive and irreversible neuronal loss and cognitive decline. The macrophages of the central nervous system (CNS) belong to the innate immune system and comprise parenchymal microglia and CNS-associated macrophages (CAMs) at the CNS interfaces (leptomeninges, perivascular space and choroid plexus). Microglia and CAMs have received attention as they may play a key role in disease onset and progression e. g., by clearing amyloid beta (Aβ) through phagocytosis. Genome-wide association studies (GWAS) have revealed that human microglia and CAMs express numerous risk genes for AD, further highlighting their potentially critical role in AD pathogenesis. Microglia and CAMs are tightly controlled by environmental factors, such as the host microbiota. Notably, it was further reported that the composition of the gut microbiota differed between AD patients and healthy individuals. Hence, emerging studies have analyzed the impact of gut bacteria in different preclinical mouse models for AD as well as in clinical studies, potentially enabling promising new therapeutic options.