Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity

Amyloid-beta (A beta) peptides are the main components of the plaques found in the brains of patients with Alzheimer's disease. However, A beta peptides are also detectable in secretory compartments and peripheral blood contains a complex mixture of more than 40 different modified and/or N- and C-terminally truncated A beta peptides. Recently, anti-infective properties of A beta peptides have been reported. Here, we investigated the interaction of A beta peptides of different lengths with various bacterial strains and the yeast Candida albicans. The amyloidogenic peptides A beta(1-42), A beta(2-42), and A beta(3p-42) but not the non-amyloidogenic peptides A beta(1-40) and A beta(2-40) bound to microbial surfaces. As observed by immunocytochemistry, scanning electron microscopy and Gram staining, treatment of several bacterial strains and Candida albicans with A beta peptide variants ending at position 42 (A beta(x-42)) caused the formation of large agglutinates. These aggregates were not detected after incubation with A beta(x-40). Furthermore, A beta(x-42) exerted an antimicrobial activity on all tested pathogens, killing up to 80% of microorganisms within 6 h. A beta(1-40) only had a moderate antimicrobial activity against C. albicans. Agglutination of A beta(1-42) was accelerated in the presence of microorganisms. These data demonstrate that the amyloidogenic A beta(x-42) variants have antimicrobial activity and may therefore act as antimicrobial peptides in the immune system.