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More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer\u2019s disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li<jats:sub>2<\/jats:sub>CO<jats:sub>3<\/jats:sub>). We found that LISPRO (8-week oral treatment) reduces <jats:italic>\u03b2<\/jats:italic>-amyloid plaques and phosphorylation of tau by reducing neuroinflammation and inactivating glycogen synthase kinase 3<jats:italic>\u03b2<\/jats:italic> in transgenic Tg2576 mice. Specifically, cytokine profiles from the brain, plasma, and splenocytes suggested that 8-week oral treatment with LISPRO downregulates pro-inflammatory cytokines, upregulates anti-inflammatory cytokines, and suppresses renal cyclooxygenase 2 expression in transgenic Tg2576 mice. Pharmacokinetic studies indicated that LISPRO provides significantly higher brain lithium levels and more steady plasma lithium levels in both B6129SF2\/J (2-week oral treatment) and transgenic Tg2576 (8-week oral treatment) mice compared with Li<jats:sub>2<\/jats:sub>CO<jats:sub>3<\/jats:sub>. Oral administration of LISPRO for 28 weeks significantly reduced <jats:italic>\u03b2<\/jats:italic>-amyloid plaques and tau-phosphorylation. In addition, LISPRO significantly elevated pre-synaptic (synaptophysin) and post-synaptic protein (post synaptic density protein 95) expression in brains from transgenic 3XTg-AD mice. Taken together, our data suggest that LISPRO may be a superior form of lithium with improved safety and efficacy as a potential new disease modifying drug for AD.<\/jats:p>","DOI":"10.1038\/cddis.2017.279","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T12:43:39Z","timestamp":1497530619000},"page":"e2880-e2880","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["RETRACTED ARTICLE:LISPRO mitigates \u03b2-amyloid and associated pathologies in Alzheimer\u2019s mice"],"prefix":"10.1038","volume":"8","author":[{"given":"Ahsan","family":"Habib","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrell","family":"Sawmiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Rongo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huayan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengnuo","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Giunta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Currier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas Ronald","family":"Shytle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,15]]},"reference":[{"key":"BFcddis2017279_CR1","doi-asserted-by":"publisher","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","volume":"82","author":"CL Masters","year":"1985","unstructured":"Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K . 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