Molecular Neurobiology

, Volume 54, Issue 4, pp 2869–2877 | Cite as

Altered Long Noncoding RNA Expression Precedes the Course of Parkinson’s Disease—a Preliminary Report

  • Theo F. J. KrausEmail author
  • Melanie Haider
  • Judith Spanner
  • Martina Steinmaurer
  • Vanessa Dietinger
  • Hans A. Kretzschmar


Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that affects approximately seven million patients worldwide. Despite intensive research, the molecular mechanisms initiating and promoting PD are still unknown. However, it is assumed that environmental factors trigger PD. Recent research demonstrated that long noncoding RNAs (lncRNA) interfere in transcriptional and translational processes modulating gene expression reflecting environmental influences. Nevertheless, there is no systematic analysis available that investigates the impact of lncRNAs on PD. In the current study, we performed a comprehensive analysis on expression levels of 90 well-annotated lncRNAs in 30 brain specimens deriving from 20 PD patients and 10 controls as a preliminary report on the significance of lncRNAs in PD. Expression profiling of lncRNAs revealed that five lncRNAs are significantly differentially expressed in PD. While H19 upstream conserved 1 and 2 is significantly downregulated in PD, lincRNA-p21, Malat1, SNHG1, and TncRNA are significantly upregulated. An analysis on expression levels and PD stages revealed that the identified dysregulated lncRNA are altered already in early disease stage and that they precede the course of PD. In summary, this is the first comprehensive analysis on lncRNAs in PD revealing significantly altered lncRNAs. Additionally, we found that lncRNA dysregulations precede the course of the disease. Thus, the five newly identified lncRNAs may serve as potential new biomarkers appropriate even in early PD. They may be used in monitoring disease progression and they may serve as potential new targets for novel therapeutic approaches.


Parkinson’s disease PD Long noncoding RNA lncRNA Human brain tissue 



We thank the Neurobiobank Munich (Thomas Arzberger) for providing human brain tissue.

Compliance with Ethical Standards


This work was supported by the German Federal Ministry of Education and Research (BMBF) through the EpiPD (Epigenomics of Parkinson’s disease) project, under the auspices of the bilateral BMBF/ANR (French National Research Agency) Epigenomics of Common and Age-related Diseases Programme (grant no. 01KU1403B to TFJK and HAK) and by the BMBF through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant no. 01ZX1314I to TFJK and HAK).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2016_9854_MOESM1_ESM.xlsx (19 kb)
Table S1 Overview on the expression stability of all 90 analysed lncRNAs. Indicated are stability values, intragroup and intergroup variations as calculated using the NormFinder algorithm. Stability values of ≤ 0.009 and CT values of ≤ 32 are indicated in grey. Only the 3 lncRNAs GAS5-family, HAR1B and SNHG4 that are indicated in grey fulfill the requirements of valid normalisers. (XLSX 18 kb)
12035_2016_9854_MOESM2_ESM.xlsx (17 kb)
Table S2 Relative expression levels of lncRNAs. Indicated are the relative expression levels of 87 unstably expressed lncRNAs as calculated using the comparative CT method. As references, we used the three stably expressed lncRNAs GAS5-family, HAR1B and SNHG4. Only 5 lncRNAs showed significant expression differences with p-values of < 0.05 (indicated in grey) in PD compared with controls: H19 upstream conserved 1 and 2, lincRNA-p21, Malat1, SNHG1, and TncRNA (indicated in grey). (XLSX 17 kb)
12035_2016_9854_MOESM3_ESM.xlsx (9 kb)
Table S3 Expression levels of candidate lncRNAs in PD stages. Classifying PD cases according to McKeith enables us to perform PD stage dependent analysis. Indicated are mean relative expression levels of the 5 identified candidate lncRNAs H19 upstream conserved 1 and 2, lincRNA-p21, Malat1, SNHG1, and TncRNA in controls, brain stem type PD, limbic type PD and neocortical type PD. (XLSX 9 kb)
12035_2016_9854_Fig4_ESM.gif (719 kb)
Figure S1

Stably expressed lncRNAs. Indicated are the expression levels of the 3 identified valid lncRNA normalisers GAS5-family, HAR1B and SNHG4. Displayed are the CT values. Indicated are mean and SEM. (GIF 719 kb)

12035_2016_9854_MOESM4_ESM.tif (516 kb)
High resolution image (TIF 516 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Theo F. J. Kraus
    • 1
    Email author
  • Melanie Haider
    • 1
  • Judith Spanner
    • 1
  • Martina Steinmaurer
    • 1
  • Vanessa Dietinger
    • 1
  • Hans A. Kretzschmar
    • 1
  1. 1.Center for Neuropathology and Prion Research (ZNP)Ludwig-Maximilians-UniversitätMunichGermany

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