INTRODUCTION: The amyloid hypothesis postulates that the main cause of Alzheimer’s disease (AD) is amyloidogenic cleavage of amyloid precursor protein (APP) and deposition of amyloid‑beta. Recently, another hypothesis was formulated that neuroinflammation may precede amyloid generation in AD development. It was also demonstrated that systemic inflammation may impair brain homeostasis and function. AIM(S): Based on these data we hypothesized that systemic inflammation impairs brain homeostasis and leads to neuroinflammation that later causes AD development. METHOD(S): To verify this hypothesis, we compared effects of systemic inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) in transgenic mice expressing human APP with Swedish AD-causing mutation (APPswe) to untreated APPswe mice. To assess AD neuropathological hallmarks, brain tissue from 4, 8, and 12‑month old animals were analyzed by immunohistochemical staining and immunoblotting. RESULTS: We found that LPS shortly after peripheral administration to APPswe mice induced astrogliosis and dysregulation of pro- and anti-inflammatory cytokines in brains already in young 4‑month old animals and these effects were also detected in 8-month old mice. In control mice not treated with APPswe, the development of signs of neuroinflammation was slower. We also compared the signs of neuroinflammation in the hippocampus and entorhinal cortex to levels of APP full-length protein and its pathologically truncated CTFs forms. CONCLUSIONS: Obtained results indicate that systemic inflammation accelerates and intensifies neuroinflammation as reflected by astrogliosis and pro-inflammatory reaction during AD development. It suggests that systemic inflammation can be considered as a common civilization risk factor of AD progression. These data became the reference for the next hypothesis and studies of our group (abstracts by A. Mietelska‑Porowska and by A. Więckowska). FINANCIAL SUPPORT: Financed by National Science Center grants no. 2014/15/D/NZ4/04361, 2018/29/N/ NZ7/01724.