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Considering the increased aging population and life expectancy, the incidence of AD will continue to rise in the following decades. However, the molecular pathogenesis of AD remains controversial, superior blood-based biomarker candidates for early diagnosis are still lacking, and effective therapeutics to halt or slow disease progression are urgently needed. As powerful genetic regulators, microRNAs (miRNAs) are receiving increasing attention due to their implications in the initiation, development, and theranostics of various diseases, including AD. In this review, we summarize miRNAs that directly target microtubule-associated protein tau (MAPT), amyloid precursor protein (APP), and \u03b2-site APP-cleaving enzyme 1 (BACE1) transcripts and regulate the alternative splicing of tau and APP. We also discuss related kinases, such as glycogen synthase kinase (GSK)-3\u03b2, cyclin-dependent kinase 5 (CDK5), and death-associated protein kinase 1 (DAPK1), as well as apolipoprotein E, that are directly targeted by miRNAs to control tau phosphorylation and amyloidogenic APP processing leading to A\u03b2 pathologies. Moreover, there is evidence of miRNA-mediated modulation of inflammation. Furthermore, circulating miRNAs in the serum or plasma of AD patients as noninvasive biomarkers with diagnostic potential are reviewed. In addition, miRNA-based therapeutics optimized with nanocarriers or exosomes as potential options for AD treatment are discussed.<\/jats:p>","DOI":"10.3390\/ijms242216259","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:35:52Z","timestamp":1699864552000},"page":"16259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Long","family":"Wang","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindong","family":"Shui","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Diao","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duoting","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-1478","authenticated-orcid":false,"given":"Tae Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41586-018-0457-8","article-title":"Facing up to the global challenges of ageing","volume":"561","author":"Partridge","year":"2018","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. 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