Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by pathological hallmarks including β-amyloid（Aβ）deposition, tau protein tangles,and neuroinflammation. The traditional theory proposed that Aβ is a pathogenic substance in the pathological process of AD. However, recent studies have found that Aβ may be an ancient natural immune effector with antibacterial functions. In this review, we summarized the research progress on the interaction phenomena and mechanisms between Aβ and lipopolysaccharide (LPS), including the evidence that Aβ has antimicrobial activity such as direct antibacterial activity, promotion of pathogen aggregation, and immune regulation. We also analyzed the support of these findings for the hypothesis of“Aβ antimicrobial and protection hypothesis”and discussed the therapeutic strategies of regulating Aβ levels or targeting infections. These new insights may expand the understanding of the pathogenesis of AD and provide an important theoretical basis and potential intervention targets for the development of innovative therapeutic methods.