Amyloid-ß is a sticky peptide notorious for forming destructive plaques in the brains of Alzheimer's disease patients, but a new study suggests that it may also serve a protective function as an antimicrobial peptide. Researchers show that fibrous nets of amyloid-ß can ensnare invading microbes, halting infection in mouse and worm models of Alzheimer's disease. The findings raise intriguing questions about whether an overactive immune response by amyloid-ß, either to a real or perceived microbial threat, can trigger disease. A better understanding of the peptide's role in the brain's immune system may open new therapeutic avenues for Alzheimer's disease, the researchers say. Amyloid-ß is widely viewed as an abnormal byproduct of cells, but whether the peptide, which is conserved across many species throughout evolution, has a normal function remains unclear. Recent research revealed that it exhibits strong antimicrobial activity to clinically relevant pathogens in vitro. Here, Deepak Kumar Vijaya Kumar and colleagues show that amyloid-ß can protect against bacterial and fungal infection in nematodes and mice in vivo. Mice that overexpressed the peptide showed greater resistance to bacterial infection, with improved survival compared to normal mice or mice unable to produce amyloid-ß. In mice with Alzheimer's disease, injecting Salmonella typhimurium into the brain stimulated and accelerated amyloid-ß to cluster around the bacteria. Amyloid-ß fibrils seemed to form nets that captured and entrapped bacterial cells to prevent infection, a mechanism similar to that used by known antimicrobial peptides. Altogether, the findings cast amyloid-ß in new light as a peptide with dual protective and damaging functions, prompting re-examination of the role of infection in Alzheimer's disease.
Science Translational Medicine