Alzheimer's disease-associated amyloid β (Aβ) protein is shown to function as an antimicrobial peptide (AMP) in the innate immune system. The study demonstrates that Aβ exhibits antimicrobial activity against eight common pathogens, with potency comparable to or greater than that of LL-37, a well-known human AMP. Aβ is found to have higher antimicrobial activity in brain homogenates from Alzheimer's patients compared to non-AD samples, and this activity is correlated with Aβ levels. Immunodepletion of Aβ from brain homogenates ablates antimicrobial activity, supporting a direct role for Aβ in this function. The findings challenge the prevailing view that Aβ is merely a byproduct with no physiological role, suggesting instead that it may play a protective role in the innate immune system by combating microbial infections. This has important implications for understanding Alzheimer's pathology and developing new treatment strategies. The study also highlights the potential for Aβ to contribute to neuroinflammation and suggests that immune responses, including those involving Aβ, may be involved in the disease process. The research underscores the need to re-evaluate the role of Aβ in immune function and its potential involvement in both infectious and non-infectious diseases.Alzheimer's disease-associated amyloid β (Aβ) protein is shown to function as an antimicrobial peptide (AMP) in the innate immune system. The study demonstrates that Aβ exhibits antimicrobial activity against eight common pathogens, with potency comparable to or greater than that of LL-37, a well-known human AMP. Aβ is found to have higher antimicrobial activity in brain homogenates from Alzheimer's patients compared to non-AD samples, and this activity is correlated with Aβ levels. Immunodepletion of Aβ from brain homogenates ablates antimicrobial activity, supporting a direct role for Aβ in this function. The findings challenge the prevailing view that Aβ is merely a byproduct with no physiological role, suggesting instead that it may play a protective role in the innate immune system by combating microbial infections. This has important implications for understanding Alzheimer's pathology and developing new treatment strategies. The study also highlights the potential for Aβ to contribute to neuroinflammation and suggests that immune responses, including those involving Aβ, may be involved in the disease process. The research underscores the need to re-evaluate the role of Aβ in immune function and its potential involvement in both infectious and non-infectious diseases.