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Extracellular vesicles (EVs) have emerged as promising biomarkers for neurodegeneration, owing to their accessibility in bodily fluids and dynamic molecular cargo, including microRNAs (miRNAs). The last decade has seen accumulating evidence for miRNA dysregulation in circulating EVs from people with neurodegenerative diseases; however, assessing reproducibility between studies remains challenging, largely due to clinical and methodological heterogeneity. In this systematic review, we comprehensively searched the MEDLINE database for studies investigating miRNA expression in biofluids from people with neurodegenerative diseases. We extracted miRNA expression data from 185 peer\u2010reviewed publications, published until June of 2025, reporting altered miRNA levels in fluid\u2010derived EVs from people with neurodegenerative diseases. We consolidated results between studies to identify the most frequently dysregulated miRNAs across diseases, with a focus on Alzheimer's disease, Parkinson's disease, mild cognitive impairment, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, stroke, traumatic brain injury, and schizophrenia. Evaluating tissue specificity of frequently dysregulated miRNAs revealed enrichment of select miRNAs in the nervous system relative to blood and immune compartments. Summarizing miRNA regulation across biofluids emphasized consistencies between cerebrospinal fluid and plasma, but not serum. We highlight circulating miRNAs that may be reflective of neuropathology, including miR\u2010143\u20103p, miR\u2010127\u20103p, miR\u20109\u20105p, miR\u201015a\u20105p, and miR\u2010125b\u20105p. Finally, we provide a repository of miRNA expression data from over 30 neurodegenerative conditions which can be exploited to further investigate miRNA regulation in diseases of interest.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70323-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70323","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:22:35Z","timestamp":1769145755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Extracellular Vesicle\u2010Derived\n                    <scp>microRNAs<\/scp>\n                    as Fluid Biomarkers in Neurodegenerative Diseases: A Systematic Review"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9926-3227","authenticated-orcid":false,"given":"Aliyah","family":"Zaman","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sienna S.","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University  Montreal Quebec Canada"},{"name":"The Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyson 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