Abstract
Despite the enormous literature documenting the importance of amyloid beta (Aβ) protein in Alzheimer’s disease, we do not know how Aβ aggregation is initiated and why it has its unique distribution in the brain. In vivo and in vitro evidence has been developed to suggest that functional microbial amyloid proteins produced in the gut may cross-seed Aβ aggregation and prime the innate immune system to have an enhanced and pathogenic response to neuronal amyloids. In this commentary, we summarize the molecular mechanisms by which the microbiota may initiate and sustain the pathogenic processes of neurodegeneration in aging.
Highlights
The original descriptions of cortical plaques in subjects with dementia was provided by several scientists, including Emil Redlich (1898), Koichi Miyake (1906), Alois Alzheimer (1906), Oskar Fischer (1907), and Soloman Carter Fuller (1907) [1]
The molecular analysis of the material in the plaque was not clarified until Glenner and Wong (1984) described the amino acid sequence of the amyloid which they found to have no homology to any known protein
Mutations in amyloid precursor protein (APP) have been found to be a genetic cause of early-onset Alzheimer’s disease (AD). This led to the “amyloid hypothesis”, which posited that accumulation of the Aβ protein in the brain is responsible for the pathogenesis of AD [2,3]
Summary
The original descriptions of cortical plaques in subjects with dementia was provided by several scientists, including Emil Redlich (1898), Koichi Miyake (1906), Alois Alzheimer (1906), Oskar Fischer (1907), and Soloman Carter Fuller (1907) [1]. In 2015, Friedland proposed that bacterial amyloid may cross-seed the aggregation of neuronal proteins such as Aβ, alpha synuclein (AS), tau and others to initiate a prion-like propagation [10]. This process may begin with enteroendocrine and M cells in the gut epithelium and be transmitted to the brain through the autonomic nervous system via a bidirectional pathway (the gut-brain axis, [11,12]). Perov et al discovered structural similarity between the fibers of the best studied bacterial amyloid protein curli, and neuronal amyloids [14] They noted that the curli protein CsgA cross-seeds the fibrillation of Aβ, as was previously proposed [10]. It should be noted that these studies were done in vitro with nonbiological buffers, suggesting a need for in vivo studies using simple systems such as yeast or C. elegans to demonstrate this process
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