Volume 19, Issue 6 p. 2618-2632
ALTERNATE FORMAT RESEARCH ARTICLE

Blood RNA transcripts reveal similar and differential alterations in fundamental cellular processes in Alzheimer's disease and other neurodegenerative diseases

Carol J. Huseby

Corresponding Author

Carol J. Huseby

ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA

Correspondence

Carol J. Huseby, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ 85281, USA.

E-mail: [email protected]

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Elaine Delvaux

Elaine Delvaux

ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA

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Danielle L. Brokaw

Danielle L. Brokaw

University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA

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Paul D. Coleman

Paul D. Coleman

ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA

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First published: 21 December 2022
Citations: 4

Abstract

Background

Dysfunctional processes in Alzheimer's disease and other neurodegenerative diseases lead to neural degeneration in the central and peripheral nervous system. Research demonstrates that neurodegeneration of any kind is a systemic disease that may even begin outside of the region vulnerable to the disease. Neurodegenerative diseases are defined by the vulnerabilities and pathology occurring in the regions affected.

Method

A random forest machine learning analysis on whole blood transcriptomes from six neurodegenerative diseases generated unbiased disease-classifying RNA transcripts subsequently subjected to pathway analysis.

Results

We report that transcripts of the blood transcriptome selected for each of the neurodegenerative diseases represent fundamental biological cell processes including transcription regulation, degranulation, immune response, protein synthesis, apoptosis, cytoskeletal components, ubiquitylation/proteasome, and mitochondrial complexes that are also affected in the brain and reveal common themes across six neurodegenerative diseases.

Conclusion

Neurodegenerative diseases share common dysfunctions in fundamental cellular processes. Identifying regional vulnerabilities will reveal unique disease mechanisms.

Highlights

  • Transcriptomics offer information about dysfunctional processes.
  • Comparing multiple diseases will expose unique malfunctions within diseases.
  • Blood RNA can be used ante mortem to track expression changes in neurodegenerative diseases.
  • Protocol standardization will make public datasets compatible.

CONFLICTS OF INTEREST

Carol Huseby and Paul Coleman filed patent application Computer-implemented method and devices for diagnosing neurodegenerative disease, provisional US patent application number 63/143,616, and patent application Algorithm to distinguish multiple neurodegenerative diseases on the basis of transcripts in the blood, provisional US patent application number 63/250,889. Elaine Delvaux and Danielle J. Brokaw have nothing to disclose. Author disclosures are available in the supporting information.