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

Autor: Huseby CJ; ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA., Delvaux E; ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA., Brokaw DL; University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Coleman PD; ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 Jun; Vol. 19 (6), pp. 2618-2632. Date of Electronic Publication: 2022 Dec 21.
DOI: 10.1002/alz.12880
Abstrakt: 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.
(© 2022 the Alzheimer's Association.)
Databáze: MEDLINE