{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:38:32Z","timestamp":1785321512073,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIA","award":["R01-AG060718"],"award-info":[{"award-number":["R01-AG060718"]}]},{"name":"NIH\/NIA","award":["RP190682"],"award-info":[{"award-number":["RP190682"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["R01-AG060718"],"award-info":[{"award-number":["R01-AG060718"]}]},{"name":"Cancer Prevention Research Institute of Texas","award":["RP190682"],"award-info":[{"award-number":["RP190682"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tacrolimus (TAC) has emerged as a potential therapy for Alzheimer\u2019s disease (AD), with the challenge of balancing its therapeutic benefits against its immunosuppressive effects. This study explores the efficacy of a sub-immunosuppressive TAC dosing regimen to ameliorate AD-related pathologies. TAC was administered daily for 14 days, with drug concentrations measured via liquid chromatography tandem mass spectrometry (LC-MS\/MS) in whole blood and hippocampal tissue from C57BL6J mice, while immunofluorescence analyses and Western blotting (performed on hippocampal extracts) were conducted in 10\u201312 month old 3xTg-AD mice to evaluate levels of tau and amyloid-beta (A\u03b2) proteins. The results from LC-MS\/MS revealed that lower TAC doses resulted in sub-immunosuppressive blood levels, while still penetrating the hippocampi. Immunofluorescence showed reductions in tau and A\u03b2 proteins in 3xTg-AD mice. Additionally, Western blot analyses revealed reductions in tau and A\u03b2, along with increases in synaptic and autophagy-related proteins. These findings highlight the potential of sub-immunosuppressive TAC doses in effectively targeting AD pathology while minimizing the risk of chronic systemic immunosuppression. Further research and clinical trials are warranted to establish the optimal TAC dosing regimen for AD treatment.<\/jats:p>","DOI":"10.3390\/ijms26051797","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T04:03:17Z","timestamp":1740024197000},"page":"1797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sub-Immunosuppressive Tacrolimus Ameliorates Amyloid-Beta and Tau Pathology in 3xTg-AD Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6231-744X","authenticated-orcid":false,"given":"Jacqueline","family":"Silva","sequence":"first","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batbayar","family":"Tumurbaatar","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutatip","family":"Guptarak","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9310-8982","authenticated-orcid":false,"given":"Anna","family":"Fracassi","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-447X","authenticated-orcid":false,"given":"Giulio","family":"Taglialatela","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"},{"name":"The Moody Brain Health Institute, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rao, Y.L., Ganaraja, B., Murlimanju, B.V., Joy, T., Krishnamurthy, A., and Agrawal, A. 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