tRNA Fragment Profiles in Patients With Parkinson's Disease

Abdullah Hashmi, MD

July 07, 2022

The study covered in this summary was published in bioRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Transfer RNA fragments (tRFs) expressed in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) are distinct from blood tRF levels and may reflect cerebral changes.

  • Higher levels of long tRFs were found in the CSF than in the blood. The CSF showed age-associated declines of the specific tRFs and more pronounced differences between sexes than did blood level tRFs.

  • Patients with PD were segregated by distinct sets of tRFs when compared with a healthy control group.

Why This Matters

  • Modified tRF blood levels have been shown in nervous system conditions, but little is known about tRF levels in the CSF in different disease states.

  • The analysis may serve as a resource to enable interested researchers to explore relevant CSF and blood tRF in the context of sex, age, and disease-related values.

Study Design

  • A short RNA-seq dataset of postmortem CSF samples from 60 patients with PD and 63 age-matched healthy controls were analyzed.

  • A larger set of blood short-RNA sequencing data from both patients with PD and healthy controls was obtained from the Progression Markers Initiative (PPMI) database.

  • For each participant, the latest of five available time points was chosen and only samples with RNA integrity number (RIN) ≥ 6 were introduced into the analysis.

Key Results

  • Higher levels of long tRFs were found in the CSF than in the blood in patients with PD. Distinct sets of tRFs in the CSF and in the blood segregated patients with PD from controls.

  • The CSF showed pronounced age-associated declines of level of nuclear genome originated 3'-tRFs and i-tRFs, and far lower decline of mitochondrial genome-originated tRFs. The blood showed moderate elevation of 3'-tF level with age.

  • More pronounced differences of tRFs exist between the sexes. Both CSF and blood present modified levels of tRFs in a sex-, age-, and disease-related manner.

  • An enrichment of tRFs predicted to target cholinergic mRNAs were found to be predominantly mitochondrial originated, indicating a possibility of mitochondrial impairment leading to deregulation of cholinergic tone.

  • The CSF expressed TRFs are not a mirror of blood tRFs but rather likely reflect cerebral changes.

Limitations

  • Specific limitations of the study were not discussed.

Disclosures

  • The study was supported by the Israel Science Foundation, the American Friends of the Hebrew University of Jerusalem, and the Leopold Sara and Norman Israel Fund, as well as Sephardic Home for the Aged for grants for Madrer and Vaknine-Treidel.

  • Data for the PPMI database is supported by a public-private partnership and includes support from the Michael J. Fox Foundation for Parkinson's Research, as well as several pharmaceutical, bioscience, and therapeutic companies.

This is a summary of a preprint research study, " Cerebrospinal Fluid and Blood Profiles of Transfer RNA Fragments Show Age, Sex and Parkinson's Disease–Related Changes ," written by researchers at Rambam Health Care Campus, Neurosurgery Department, Haifa, Israel and both the Edmond and Lily Safra Center for Brain Sciences and Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, on bioRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on bioRxiv.org.

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