Summary: Several neurodegenerative disorders share the same underlying dysfunctional cellular processes.

Source: University of Arizona

Confusing neurodegenerative diseases are known to attack different regions of the brain, causing severe cognitive and motor deficits. These (generally fatal) diseases have taken a toll on society.

New insights suggest that most of these pains have their origins in a set of common processes, which play out differently as each disease develops.

In the study shown in the current issue Alzheimer’s and Dementia: Journal of the Alzheimer’s AssociationAuthor Carol Huseby of Arizona State University and her colleagues looked at changes in six different neurodegenerative disorders: amyotrophic lateral sclerosis or Lou Gehrig’s disease, Alzheimer’s disease, Friedreich’s ataxia, frontotemporal dementia, Huntington’s disease, and Parkinson’s disease. With the ASU-Banner Neurodegenerative Disease Research Center.

The research uses a new approach that involves machine learning analysis of RNA in whole blood. By comparing multiple diseases, researchers can identify which RNA markers occur in several neurodegenerative diseases and which are unique to each disease.

“Many neurodegenerative diseases seem to share the same underlying dysfunctional cellular processes,” said Huseby, a researcher at the ASU-Banner Neurodegenerative Disease Research Center.

“Differences between diseases may be key to finding regional cell type vulnerabilities and therapeutic targets for each disease.”

The blood samples used for the study were obtained from a public data set called the Gene Expression Omnibus. Each of the six neurodegenerative diseases was investigated. As the machine learning algorithm sifted through thousands of genes, it collected RNA transcripts that neatly categorized each disease.

The selected RNA transcripts show eight common themes in the six neurodegenerative diseases: transcriptional regulation, degradation (a process in inflammation), immune response, protein synthesis, cell death or apoptosis, cytoskeletal components, ubiquitination/proteasome (involved in protein degradation). and mitochondrial complexes (which control energy use in cells). The eight unmasked cellular deficits are associated with detectable diseases in the brain of each disease.

The study also identified abnormal transcripts for each disease, which may indicate unexplored disease pathways. Such disease-specific outliers can serve as a source of diagnostic biomarkers.

For example, although synaptic loss is a common feature in the six diseases analyzed, transcripts related to a phenomenon known as spliceosome regulation were found only in the case of Alzheimer’s disease. (The spliceosome is a protein complex found in the cell nucleus that is essential for proper cell function. Defective RNA is associated with disease.)

Blood biomarkers for the diagnosis of neurodegenerative diseases, combined with powerful statistical methods using artificial intelligence, have opened a new window on these serious problems. Blood can be easily sampled from living patients at all stages of health and disease, providing a powerful new tool for early diagnosis.

According to the United Nations, when all neurodegenerative diseases are considered, the global death toll may exceed 1 billion people. The course of many of these diseases is long and painful, which not only causes severe suffering to patients, but also causes a great economic burden on health care systems.

New early detection methods, improved treatments, and potential prevention strategies are essential.

Most neurodegenerative diseases, however, are difficult to accurately diagnose and stubbornly resist treatment, including Alzheimer’s disease (AD), the leading cause of dementia.

In AD Although genetic factors play a role in the development, most cases are considered rare, and the causes are unclear.

This shows the pattern of the brain
The diagram shows the cell types and brain regions affected by six different neurodegenerative diseases: Friedreich’s ataxia (purple); Huntington’s disease (blue); Frontal amnesia (yellow); Amyotrophic lateral sclerosis (ALS), as well as motor neurone disease (MND) or Lou Gehrig’s disease (Green); Parkinson’s disease (orange); and Alzheimer’s disease (pink). Credit: Shireen Dooling

This is also true of three other diseases highlighted in the study: frontotemporal dementia, ALS and Parkinson’s disease. Huntington’s disease and Friedreich’s ataxia appear to be genetically determined and are said to be familial.

Signs of neurodegeneration are identified in both the central nervous and peripheral vascular systems. The disorders can spread from their source to distant brain regions, causing most of their damage.

The study describes RNA clusters, or trees, selected by a machine learning process, which show gene expression common to the six neurodegenerative diseases explored in the study, and distinct and disease-specific profiles.

Thousands of such trees were generated by a machine learning algorithm to select a group of 20 transcripts that best corresponded to known disease pathways in the diseases under study and compared statistically.

The findings provide clues about common cellular properties that may play a role in the jump-start process in neurodegeneration. The study also raises puzzling questions about how these common substances can cause various diseases.

About 10,000 genes were expressed from the RNA transcripts extracted from the blood. A machine learning algorithm, known as Random Forest, classifies the data and matches results to gene expression profiles known to be associated with disease-related biological pathways.

Screening whole blood and testing the complete RNA profile can overcome the limitations of many other types of tests, which are often extensive and expensive, highly invasive and labor intensive.

look up

This book shows a little girl with a teddy bear

A blood test, on the other hand, can be performed anywhere in the world at a low cost. Blood results can be monitored over time, providing a valuable window into disease progression. This type of research can lead to new treatments.

The results suggest a strong possibility: transcriptional changes shared by many types of disease may provide the first seeds that later develop into each specific brain disorder. The mechanisms underlying these common factors to produce different diseases and symptoms, which target different brain regions, remain a central puzzle to be solved.

Future studies will examine the transcriptional effects on neurons in addition to blood cells, as well as the underlying mechanisms underlying the development of neurodegenerative diseases and the development of specific pathologies.

So Neuroscience and Genetics Research News

Author: Press office
Source: University of Arizona
Contact: Press Office – University of Arizona
Image: Image credited to Shirin Dolling.

Preliminary study: Closed access.
Blood RNA transcripts reveal similar and unique changes in basic cellular processes in Alzheimer’s disease and other neurodegenerative diseases.” by Carol J. Huseby et al. Alzheimer’s and dementia


Draft

Blood RNA transcripts reveal similar and unique changes in basic cellular processes in Alzheimer’s disease and other neurodegenerative diseases.

Background

Defective processes in Alzheimer’s disease and other neurodegenerative diseases cause neurodegeneration in the central and peripheral nervous systems. Research shows that any type of neurodegeneration is a systemic disease that can start even outside the susceptible region. Neurodegenerative diseases are characterized by exposure and pathology in the affected regions.

method

Random forest machine learning analysis of whole blood transcriptomes from six neurodegenerative diseases generated unbiased disease-classifying RNA transcripts.

Results

We report that selected transcriptomes for each neurodegenerative disease represent fundamental biological cell processes, including transcriptional regulation, degeneration, immune response, protein synthesis, apoptosis, cytoskeletal components, ubiquitylation/proteasome, and mitochondrial fusion. Brain and shows common themes in six neurodegenerative diseases.

Conclusion

Neurodegenerative diseases share common defects in basic cellular processes. Identifying regional exposures reveals unique disease mechanisms.

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