Although amyloid-beta protein has been thoroughly researched as a key player in the neuropathology of Alzheimer's disease, its normal, physiological role has heretofore been unknown. In this extensive study by Kumar and colleagues, a wealth of data from transgenic mouse, nematode, and cell culture models are presented; collectively, these data suggest that amyloid-beta may serve an antimicrobial function designed to protect the brain from invading pathogens.
| In the first set of experiments, the authors found that, versus nontransgenic controls, mice genetically modified to produce amyloid-beta are protected from infection, encephalomyelitis, and mortality induced by Salmonella Typhimurium bacteria. Next, it was shown that the nematode, Caenorhabditis elegans, was protected from infection and mortality caused by either Salmonella Typhimurium or the yeast pathogen Candida albicans when genetically designed to produce amyloid-beta. The authors confirmed the protective effects of amyloid-beta in cell cultures using 2 different cell lines (human brain neuroglioma) and Chinese hamster ovary cells) transformed to produce amyloid beta (as well as non-transformed control cells). In these cell culture experiments, production of amyloid-beta (most notably amyloid-beta-42) offered significant protection from C. albicans-induced death, and this increased survival of host cells was mediated by a decreased adhesion of microbes to the host cell as well as increased agglutination of C. albicans microbial cells. |
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Furthermore, using all 3 models (mice, nematode, and cell culture), the research team determined that these antimicrobial actions of amyloid-beta are arbitrated via binding of amyloid-beta oligomers to carbohydrates found on microbial cell walls. Following binding to these carbohydrates, amyloid-beta forms fibrils that essentially tie up and sequester microbial cells (ie, agglutination), preventing the adherence of microbial cells to host cells and halting microbial infection (See figure). These exciting new data not only provide a physiological function for amyloid-beta, but warrant further investigation into the role of infection in the etiology of Alzheimer's disease.
>> Kumar DKV, Choi SH, Washicosky KJ et al. Sci Transl Med 2016;8(340):340ra72./a>