{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:26:38Z","timestamp":1789165598119,"version":"build-2803163510"},"reference-count":484,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AG075897-05"],"award-info":[{"award-number":["1R01AG075897-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1R01AG075897-05"],"award-info":[{"award-number":["1R01AG075897-05"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and significant neuropathological changes. Early and accurate diagnosis remains a major challenge, highlighting the need for reliable, minimally invasive biomarkers. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as promising candidates. Their expression is altered in the brains of AD patients, reflecting disease-specific pathological processes, and they are detectable in peripheral biofluids. However, discrepancies in miRNA profiles between the brain and the circulation, and between patient populations remain a significant limitation, raising questions about their origin, transport across the blood\u2013brain barrier, and their reliability in reflecting central nervous system pathology. This review provides a comprehensive overview of current research comparing miRNA expression profiles in brain tissue and blood in AD, with a focus on their biological relevance, mechanisms of release and transport, and diagnostic potential. We also discuss the challenges associated with cross-tissue variability, methodological inconsistencies, and the need for standardized approaches. Finally, we highlight future directions, including multi-tissue analyses and integration with other noninvasive modalities, to improve the clinical utility of miRNA-based biomarkers in AD.<\/jats:p>","DOI":"10.3390\/ijms27135990","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:33:06Z","timestamp":1783089186000},"page":"5990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Peripheral and Central miRNA Signatures in Alzheimer\u2019s Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers"],"prefix":"10.3390","volume":"27","author":[{"given":"Amy S.","family":"Shiyab","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Kent State University, Kent, OH 44140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8115-0347","authenticated-orcid":false,"given":"Erin G.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH 44242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E1534","DOI":"10.1016\/S2214-109X(24)00264-X","article-title":"The global macroeconomic burden of Alzheimer\u2019s disease and other dementias: Estimates and projections for 152 countries or territories","volume":"12","author":"Chen","year":"2024","journal-title":"Lancet Glob. 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