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However, most studies induce relatively high systemic inflammation, not directly compared with the more common low\u2010grade inflammatory events experienced in humans during the life course. Using mice, we investigated the effects of low\u2010grade systemic inflammation during an otherwise healthy early life, and how this may precondition the onset and severity of Alzheimer's disease (AD)\u2010like pathology. Our results indicate that low\u2010grade systemic inflammation induces sub\u2010threshold brain inflammation and promotes microglial proliferation driven by the CSF1R pathway, contrary to the effects caused by high systemic inflammation. In addition, repeated systemic challenges with low\u2010grade LPS induce disease\u2010associated microglia. Finally, using an inducible model of AD\u2010like pathology (Line 102 mice), we observed that preconditioning with repeated doses of low\u2010grade systemic inflammation, prior to APP induction, promotes a detrimental effect later in life, leading to an increase in A\u03b2 accumulation and disease\u2010associated microglia. These results support the notion that episodic low\u2010grade systemic inflammation has the potential to influence the onset and severity of age\u2010related neurological disorders, such as AD.<\/jats:p>","DOI":"10.1002\/glia.24532","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T07:48:36Z","timestamp":1712735316000},"page":"1340-1355","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Low\u2010grade systemic inflammation stimulates microglial turnover and accelerates the onset of Alzheimer's\u2010like pathology"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-3608","authenticated-orcid":false,"given":"Monica","family":"Guerrero\u2010Carrasco","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of Southampton, Southampton General Hospital  Southampton 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