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Small RNA modifications in Alzheimer's disease
Xudong Zhang1, Fatima Trebak2, Lucas A C Souza2
1Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA.
Neurobiology of Disease
|August 25, 2020
Summary
Small RNA modifications are altered in Alzheimer's disease (AD) brains, suggesting a role in disease development. These changes were observed in both AD and vascular dementia cases, highlighting potential epigenetic links to neurodegeneration.
Area of Science:
- Epigenetics and Molecular Biology
- Neuroscience and Neurodegenerative Diseases
Background:
- Genetic factors in Alzheimer's disease (AD) are well-studied, but epigenetic mechanisms, particularly small non-coding RNAs (sncRNAs) and their modifications, remain largely undefined.
- sncRNAs are crucial regulators of physiological and pathological processes, including aging and stress responses.
- The role of altered small RNA profiles in dementia pathogenesis is currently unknown.
Purpose of the Study:
- To investigate alterations in small RNA modifications in post-mortem brain samples from individuals with Alzheimer's disease (AD) compared to controls.
- To identify specific types of small RNAs and their modifications that are dysregulated in AD.
- To explore the presence of these alterations in cases with co-occurring vascular dementia (VaD).
Main Methods:
- Utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput analysis of small RNA modifications.
- Analyzed post-mortem prefrontal cortex samples from AD patients and healthy controls.
- Sequenced small RNA fractions (15-25 nt and 30-40 nt) to identify specific RNA species.
Main Results:
- Significant differences in small RNA modifications were observed between AD and control samples.
- The 30-40 nt RNA fraction showed enrichment for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs).
- Reductions in specific RNAs, including rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg, were detected in AD cortices.
- Most observed RNA modification alterations were present in both AD and AD with co-occurring VaD subjects.
Conclusions:
- Altered small RNA modifications represent novel molecular signals potentially implicated in Alzheimer's disease pathogenesis.
- These findings suggest a link between epigenetic dysregulation via sncRNAs and the development of AD.
- The observed changes in small RNA modifications in both AD and mixed AD/VaD cases warrant further investigation into their role in neurodegenerative processes.
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