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@ARTICLE{Derkow:140085,
      author       = {Derkow, Katja and Rössling, Rosa and Schipke, Carola and
                      Krüger, Christina and Bauer, Jakob and Fähling, Michael
                      and Stroux, Andrea and Schott, Eckart and Ruprecht, Klemens
                      and Peters, Oliver and Lehnardt, Seija},
      title        = {{D}istinct expression of the neurotoxic micro{RNA} family
                      let-7 in the cerebrospinal fluid of patients with
                      {A}lzheimer's disease.},
      journal      = {PLOS ONE},
      volume       = {13},
      number       = {7},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DZNE-2020-06407},
      pages        = {e0200602},
      year         = {2018},
      abstract     = {MicroRNAs (miRNAs) are non-coding RNAs originally involved
                      in RNA silencing and post-transcriptional regulation of gene
                      expression. We have shown in previous work that the miRNA
                      let-7b can act as a signalling molecule for Toll-like
                      receptor 7, thereby initiating innate immune pathways and
                      apoptosis in the central nervous system. Here, we
                      investigated whether different members of the miRNA family
                      let-7, abundantly expressed in the brain, are released into
                      the human cerebrospinal fluid (CSF) and whether quantitative
                      differences in let-7 copies exist in neurodegenerative
                      diseases. RNA isolated from CSF of patients with
                      Alzheimer´s disease (AD) and from control patients with
                      frontotemporal lobe dementia (FTLD), major depressive
                      episode (MDE) without clinical or neurobiological signs of
                      AD, and healthy individuals, was reverse transcribed with
                      primers against nine let-7 family members, and miRNAs were
                      quantified and analyzed comparatively by quantitative PCR.
                      let-7 miRNAs were present in CSF from patients with AD,
                      FTLD, MDE, and healthy controls. However, the amount of
                      individual let-7 miRNAs in the CSF varied substantially. CSF
                      from AD patients contained higher amounts of let-7b and
                      let-7e compared to healthy controls, while no differences
                      were observed regarding the other let-7 miRNAs. No increase
                      in let-7b and let-7e was detected in CSF from FTLD patients,
                      while in CSF from MDE patients, let-7b and let-7e copy
                      levels were elevated. In CSF from AD patients, let-7b and
                      let-7e were associated with extracellular vesicles. let-7
                      family members present in the CSF mediated neurotoxicity in
                      vitro, albeit to a variable extent. Taken together,
                      neurotoxic let-7 miRNAs are differentially and specifically
                      released in AD, but also in MDE patients. Thus, these miRNAs
                      may mirror common neuropathological paths and by this serve
                      to unscramble mechanisms of different neurodegenerative
                      diseases.},
      keywords     = {Aged / Aged, 80 and over / Alzheimer Disease: cerebrospinal
                      fluid / Cell-Derived Microparticles: metabolism / Depressive
                      Disorder, Major: cerebrospinal fluid / Female /
                      Frontotemporal Dementia: cerebrospinal fluid / Gene
                      Expression Regulation / Humans / Male / MicroRNAs:
                      cerebrospinal fluid / Middle Aged / MicroRNAs (NLM
                      Chemicals) / mirnlet7 microRNA, human (NLM Chemicals)},
      cin          = {AG Endres},
      ddc          = {610},
      cid          = {I:(DE-2719)1811005},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30011310},
      pmc          = {pmc:PMC6047809},
      doi          = {10.1371/journal.pone.0200602},
      url          = {https://pub.dzne.de/record/140085},
}