Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the
generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease.
However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis
in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial
response to Aβ peptide 1–42 (Aβ42) stimulation in vitro, in aging-associated microgliosis in vivo and in
post-mortem human samples. Compared to controls, Aβ42 markedly induced BV2 cell ROS production,
Nox2 expression, p47phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All
these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide
scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–
22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis
and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout
aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production
was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age
(61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ42
stimulation and in aging-associated microgliosis and brain inflammation
