Fig. 2

Potential mechanisms linking microbial infection with AD risks. a In the context of CNS infection, microglia recognize invading pathogens and engulf them. This activates inflammatory responses including the release of pro-inflammatory cytokines, increase of reactive oxygen species (ROS) and overactivation of nitric oxide synthase (NOS). Activated microglial cells lose homeostasis and produce more pro-inflammatory cytokines and chemokines, which help clear pathogens but also affect astrocytes and neuronal function. Alternatively, Aβ released from astrocytes and neuronal cells may act as an antimicrobial molecule after misfolding. However, the accumulation of misfolded Aβ species derived from this process may initiate AD pathology. b During peripheral infection, the excessive cytokines and chemokines present in blood infiltrate the BBB and activate microglia. Activated microglial cells lose homeostasis and produce high levels of pro-inflammatory cytokines and chemokines, activating astrocytes and damaging neurons. This cerebral inflammatory response exacerbates the deposition of Aβ in the brain parenchyma through multiple mechanisms, thus facilitating AD pathological cascades. AD: Alzheimer’s disease; Aβ: amyloid beta; BBB: blood–brain barrier; NOS: nitric oxide synthase; ROS: reactive oxygen species. Figure created using CorelDRAW