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The increased blood bacterial DNA (BB-DNA) may promote peripheral- and neuro-inflammation, contributing to cognitive impairment. MD also influences brain-derived neurotrophic factor (BDNF) production, whose alterations contribute to the etiopathogenesis of Alzheimer\u2019s disease (AD). The purpose of this study is to measure BB-DNA in healthy elderly controls (EC), and in patients with mild cognitive impairment (MCI) and AD to explore the effect on plasma BDNF levels (pBDNF), the inflammatory response, and the association with cognitive decline during a two-year follow-up. Baseline BB-DNA and pBDNF were significantly higher in MCI and AD than in EC. BB-DNA was positively correlated with pBDNF in AD, plasma Tumor necrosis factor-alpha (TNF-\u03b1), and Interleukin-10 (IL-10) levels in MCI. AD patients with BB-DNA values above the 50th percentile had lower baseline Mini-Mental State Examination (MMSE). After a two-year follow-up, AD patients with the highest BB-DNA tertile had a worse cognitive decline, while higher BB-DNA levels were associated with higher TNF-\u03b1 and lower IL-10 in MCI. Our study demonstrates that, in early AD, the higher the BB-DNA levels, the higher the pBDNF levels, suggesting a defensive attempt; BB-DNA seems to play a role in the AD severity\/progression; in MCI, higher BB-DNA may trigger an increased inflammatory response.<\/jats:p>","DOI":"10.3390\/ijms24010078","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:11:24Z","timestamp":1671603084000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bacterial DNAemia in Alzheimer\u2019s Disease and Mild Cognitive Impairment: Association with Cognitive Decline, Plasma BDNF Levels, and Inflammatory Response"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1468-2140","authenticated-orcid":false,"given":"Robertina","family":"Giacconi","sequence":"first","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5740-4733","authenticated-orcid":false,"given":"Patrizia","family":"D\u2019Aquila","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Balietti","sequence":"additional","affiliation":[{"name":"Center for Neurobiology of Aging, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8826-2467","authenticated-orcid":false,"given":"Cinzia","family":"Giuli","sequence":"additional","affiliation":[{"name":"Geriatrics Operative Unit, IRCCS INRCA, 63900 Fermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8442-1763","authenticated-orcid":false,"given":"Marco","family":"Malavolta","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7440-804X","authenticated-orcid":false,"given":"Francesco","family":"Piacenza","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8107-9061","authenticated-orcid":false,"given":"Laura","family":"Costarelli","sequence":"additional","affiliation":[{"name":"Clinical Laboratory & Molecular Diagnostics, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demetrio","family":"Postacchini","sequence":"additional","affiliation":[{"name":"Geriatrics Operative Unit, IRCCS INRCA, 63900 Fermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-9748","authenticated-orcid":false,"given":"Giuseppe","family":"Passarino","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9986-456X","authenticated-orcid":false,"given":"Dina","family":"Bellizzi","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-3002","authenticated-orcid":false,"given":"Mauro","family":"Provinciali","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grobler, C., van Tongeren, M., Gettemans, J., Kell, D.B., and Pretorius, E. 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