The study provides evidence that amyloid β-protein (Aβ), a key mediator of Alzheimer's disease (AD) pathology, functions as an antimicrobial peptide (AMP). Using in vitro assays, the researchers found that Aβ exhibits antimicrobial activity against eight common and clinically relevant microorganisms, with potency comparable to or exceeding that of LL-37, a well-known human AMP. In vivo experiments revealed that whole brain homogenates from AD patients have significantly higher antimicrobial activity compared to age-matched non-AD samples, and this activity correlates with tissue Aβ levels. The antimicrobial action was abrogated by immunodepletion of AD brain homogenates with anti-Aβ antibodies, confirming the role of Aβ. These findings suggest that Aβ may have an unrecognized function in the innate immune system, challenging current models of Aβ-mediated pathology and offering new insights into AD treatment strategies.The study provides evidence that amyloid β-protein (Aβ), a key mediator of Alzheimer's disease (AD) pathology, functions as an antimicrobial peptide (AMP). Using in vitro assays, the researchers found that Aβ exhibits antimicrobial activity against eight common and clinically relevant microorganisms, with potency comparable to or exceeding that of LL-37, a well-known human AMP. In vivo experiments revealed that whole brain homogenates from AD patients have significantly higher antimicrobial activity compared to age-matched non-AD samples, and this activity correlates with tissue Aβ levels. The antimicrobial action was abrogated by immunodepletion of AD brain homogenates with anti-Aβ antibodies, confirming the role of Aβ. These findings suggest that Aβ may have an unrecognized function in the innate immune system, challenging current models of Aβ-mediated pathology and offering new insights into AD treatment strategies.