TY  - JOUR
AU  - Derkow, Katja
AU  - Rössling, Rosa
AU  - Schipke, Carola
AU  - Krüger, Christina
AU  - Bauer, Jakob
AU  - Fähling, Michael
AU  - Stroux, Andrea
AU  - Schott, Eckart
AU  - Ruprecht, Klemens
AU  - Peters, Oliver
AU  - Lehnardt, Seija
TI  - Distinct expression of the neurotoxic microRNA family let-7 in the cerebrospinal fluid of patients with Alzheimer's disease.
JO  - PLOS ONE
VL  - 13
IS  - 7
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - DZNE-2020-06407
SP  - e0200602
PY  - 2018
AB  - 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.
KW  - Aged
KW  - Aged, 80 and over
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Cell-Derived Microparticles: metabolism
KW  - Depressive Disorder, Major: cerebrospinal fluid
KW  - Female
KW  - Frontotemporal Dementia: cerebrospinal fluid
KW  - Gene Expression Regulation
KW  - Humans
KW  - Male
KW  - MicroRNAs: cerebrospinal fluid
KW  - Middle Aged
KW  - MicroRNAs (NLM Chemicals)
KW  - mirnlet7 microRNA, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30011310
C2  - pmc:PMC6047809
DO  - DOI:10.1371/journal.pone.0200602
UR  - https://pub.dzne.de/record/140085
ER  -