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Cited by 385Extracellular vesicles in diseaseMicroRNA in disease regulationAlzheimer's disease research and treatments

Profiles of Extracellular miRNA in Cerebrospinal Fluid and Serum from Patients with Alzheimer's and Parkinson's Diseases Correlate with Disease Status and Features of Pathology

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Burgos, Kasandra, Malenica, Ivana, Metpally, Raghu, Courtright, Amanda, Rakela, Benjamin, Beach, Thomas, Shill, Holly, Adler, Charles +5 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0094839PMC PMC4010405
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Abstract

The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess disease progression and therapeutic efficacy.

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  • miR-21 was suggested to have both harmful and beneficial effects.

    “Despite its nonspecificity [33], miR-21 is considered a versatile regulator in the progression of CNS disorders [34] and was suggested to have both harmful and beneficial effects [35,36,37].”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [36]

    The Introduction discusses miRNAs generally, and the Discussion passages describe other miRNAs, but neither addresses harmful and beneficial effects of miR-21. Searches for “miR-21” and “miR-21 harmful beneficial effects” found no passage making that point in our copy. (LLM, conf=0.72)

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Authors
Burgos, K., Malenica, I., Metpally, R., Courtright, A., Rakela, B., Beach, T., Shill, H., Adler, C., Sabbagh, M., Villa, S., Tembe, W., Craig, D., & Van Keuren-Jensen, K.
Affiliations
  • Translational Genomics Research Institute (US)
  • Banner Sun Health Research Institute (US)
  • Mayo Clinic (US)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-05-05
Volume
9
Issue
5
Pages
e94839
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0094839
PMC
PMC4010405
OpenAlex
W2086412028
Cited by
385
References
3
Citations by year
2026: 9 · 2025: 28 · 2024: 30 · 2023: 28 · 2022: 44 · 2021: 39 · 2020: 47 · 2019: 40 · 2018: 36 · 2017: 33 · 2016: 25 · 2015: 21 · 2014: 4
FWCI
11.35
Type
journal article
Language
en
Update notices
correction (2014-08-13)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
Michael J. Fox Foundation for Parkinson's Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
extracellular microRNAs, Alzheimer's disease, Parkinson's disease, cerebrospinal fluid, serum, cell-free biomarkers, neurodegenerative diseases, microvesicles, RNA-binding proteins, postmortem neuropathology, Braak stages, amyloid plaques, neurofibrillary tangles, Lewy bodies, disease progression, novel miRNAs
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Parkinson Disease, MicroRNAs

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