Pathological or preventative? Amyloid-β as an effector of innate immunity

Amyloid-β (Aβ)-mediated inflammation, neurotoxicity, and plaque formation in the brain have long been regarded as pathological hallmarks of Alzheimer's disease. However, emerging evidence indicates that Aβ also serves a normal physiological role in the innate immune defense against infectious agents. A growing body of literature supports the hypothesis that Aβ is produced in response to infection and is an antimicrobial peptide-like molecule capable of inhibiting microbial growth through mechanisms such as membrane disruption and microbial entrapment. Additionally, evidence positions Aβ as an innate immune effector that can induce pro-inflammatory signals during infection. In this minireview, we discuss the clinical, in vivo, and in vitro evidence supporting the antimicrobial and innate immune effector roles of Aβ in host defense. Collectively, these findings support a broader functional role for Aβ beyond its established association with Alzheimer's disease pathology.