A perplexing range of neurodegenerative diseases are known to attack distinct regions of the brain, causing severe cognitive and motor deficit. The combined impact of these (generally fatal) diseases has inflicted a devastating toll on society. New insights suggest many of these afflictions have their origin in a constellation of common processes, which play out in different ways as each disease develops.
In a study appearing in the current issue of Alzheimer’s & Dementia: The Journal of the Alzheimer’ Association, corresponding author Carol Huseby of Arizona State University and her colleagues look at cellular alterations in six distinct neurodegenerative diseases: amyotrophic lateral sclerosis or Lou Gehrig’s disease, Alzheimer’s disease, Friedreich’s ataxia, frontotemporal dementia, Huntington’s disease and Parkinson’s disease.Carol Huseby is a researcher with the ASU-Banner Neurodegenerative Disease Research Center.
The study uses an innovative approach, which includes the machine learning analysis of RNA found in whole blood. By comparing multiple diseases, researchers can identify which RNA markers occur across several neurodegenerative diseases and which are unique to each disease.
“It appears that multiple neurodegenerative diseases harbor similar fundamental dysfunctional cellular processes,” says Huseby, a researcher with the ASU-Banner Neurodegenerative Disease Research Center. “Differences between diseases may be key to discovering regional cell-type vulnerabilities and therapeutic targets for each disease.”
The blood samples used for the study were derived from a publicly available data set known as the Gene Expression Omnibus. Each of the six neurodegenerative diseases were probed. As the machine learning algorithm combed through thousands of genes, it assembled sets of RNA transcripts that optimally classified each disease, comparing the data with RNA samples from healthy patient blood.
The selected RNA transcripts reveal eight common themes across the six neurodegenerative diseases: transcription regulation, degranulation (a process involved in inflammation), immune response, protein synthesis, cell death or apoptosis, cytoskeletal components, ubiquitylation/proteasome (involved in protein degradation) and mitochondrial complexes (which oversee energy usage in cells). The eight cellular dysfunctions uncovered are associated with identifiable pathologies in the brain characteristic of each disease.
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