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(\n                    <jats:italic>PLoS One<\/jats:italic>\n                    <jats:bold>14<\/jats:bold>\n                    , e0224433), now confirmed by other studies. Understanding how and why is of immense importance because it could represent a sea-change in how we manage patients with mild cognitive impairment through to dementia. Given that infection and\/or inflammation are likely to contribute to the development of dementias such as Alzheimer\u2019s disease (Part II of this work), we provide a historical and molecular background to how vaccines, adjuvants, and their component molecules can elicit broad-spectrum protective effects against diverse agents. We review early studies in which poxvirus, herpes virus, and tuberculosis (TB) infections afford cross-protection against unrelated pathogens, a concept known as \u2018trained immunity\u2019. We then focus on the attenuated TB vaccine, BCG, that was introduced to protect against the causative agent of TB,\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    . We trace the development of BCG in the 1920\u200as through to the discovery, by Freund and McDermott in the 1940\u200as, that extracts of mycobacteria can themselves exert potent immunostimulating (adjuvant) activity; Freund\u2019s complete adjuvant based on mycobacteria remains the most potent immunopotentiator reported to date. We then discuss whether the beneficial effects of BCG require long-term persistence of live bacteria, before focusing on the specific mycobacterial molecules, notably muramyl dipeptides, that mediate immunopotentiation, as well as the receptors involved. Part II addresses evidence that immunopotentiation by BCG and other vaccines can protect against dementia development.\n                  <\/jats:p>","DOI":"10.3233\/jad-231315","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T11:22:03Z","timestamp":1708428123000},"page":"343-360","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors"],"prefix":"10.1177","volume":"98","author":[{"given":"Charles L.","family":"Greenblatt","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel\u2013Canada (IMRIC), Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lathe","sequence":"additional","affiliation":[{"name":"Division of Infection Medicine, University of Edinburgh Medical School, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000438216.93319.ab"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-018-0062-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224433"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9050491"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2021.05.001"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000530"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.051"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.7326\/M15-0381"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-231323"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.11.038"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148291"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10101743"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00403-5"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/003591573102401109"},{"key":"e_1_3_4_16_2","first-page":"401","article-title":"Contribution \u00e0l\u2019\u00e9tude de la tuberculose exp\u00e9rimental du cobaye","volume":"21","author":"Calmette A","year":"1907","unstructured":"CalmetteA, Gu\u00e9rinC, BretonM (1907) Contribution \u00e0l\u2019\u00e9tude de la tuberculose exp\u00e9rimental du cobaye. 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