Alzheimer’s disease (AD), the most common form of dementia, affects over 55 million people globally and is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). The gut microbiome and the brain form a complex, bi-directional relationship, known as the microbiota-gut-brain axis, where communication between the gastrointestinal tract (GI) and central nervous system (CNS) plays a role in neurodegenerative diseases. Disruptions to this axis can contribute to AD pathogenesis. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. The gut microbiota as the source of a large amount of amyloid, LPS, and other toxins, may contribute to systemic inflammation and disruption of physiological barriers, allowing for the translocation of bacteria and their products from the GI tract to the CNS. Specifically, bacterial amyloids, like curli, may interact with human amyloid proteins, accelerating their deposition and aggregation in the brain. The bacterial amyloid curli may be associated with gut epithelial neuroendocrine activation, potentially impacting central Aβ pathogenesis in the AD brain.
