Alzheimer’s disease affects most of the known biological signaling pathways in the brain

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Summary: Of 341 known biological pathways, 91% are associated with Alzheimer’s disease.

Source: Beth Israel Deaconess Medical Center

In the United States, almost 6 million older adults have Alzheimer’s disease, a number expected to double by 2050.

Already the sixth leading cause of death, Alzheimer’s disease is a complex neurodegenerative disease that causes memory loss, confusion, poor judgment, depression, delusions and agitation that robs people of their ability to live independently.

At present, the biological mechanisms underlying Alzheimer’s disease are poorly understood; As a result, there are few effective treatments and no cure for the disease.

In a recent study, a research team led by scientists from Beth Israel Deaconess Medical Center (BIDMC) conducted a systematic review of more than 200,000 scientific publications to understand the breadth and diversity of biological signaling pathways — key molecular chain reactions that drive changes in effect cells. who have contributed to Alzheimer’s disease through research over the past 30 years.

The team found that although almost all known signaling pathways have been implicated in the disease, the most commonly associated biological mechanisms – including those related to the immune system, metabolism and long-term depression – are evolving despite major technological advances in the 30th century Years have not changed significantly progress.

The work of the scientists, published in Frontiers in aging neurosciencewill advance research into the mechanisms of neurodegeneration.

“The burden of Alzheimer’s disease continues to mount, propelling us toward a neurological epidemic,” said Winston A. Hide, Ph.D., director of the Core Facility for Precision RNA Medicine at BIDMC and associate professor of medicine from Harvard Medical School.

“Our results suggest that not only is this disorder incredibly complex, but that its pathology encompasses most of the known biological pathways. This means the effects of the disease in the body are much broader than we thought.”

The team performed a comprehensive text search of 206,324 publication abstracts on pathway-specific dementia published since 1990. Next, they examined 341 known biological pathways and determined how many publications linked a particular pathway to the disease.

The researchers found that 91 percent of the signaling pathways – all but seven – are linked to Alzheimer’s disease. Almost half of the signaling pathways have been linked to Alzheimer’s disease in more than 100 scientific papers.

This shows a brain
The team found that although almost all known signaling pathways have been implicated in the disease, the most commonly associated biological mechanisms – including those related to the immune system, metabolism and long-term depression – are evolving despite major technological advances in the 30th century Years have not changed significantly progress. The image is in the public domain

They also found that the 30 most commonly cited pathways in the literature have remained relatively constant over the past 30 years, suggesting that most studies of the disease have focused on a small subset of all known disease-associated pathways.

“Clinical trials aimed at either delaying the onset or slowing the progression of Alzheimer’s disease have largely failed,” said study lead author Sarah Morgan, who was a postdoctoral fellow at BIDMC during the scope of this research and now an associate professor at the Queen Mary University of London.

“Given that an unexpected diversity of signaling pathways is associated with Alzheimer’s disease, a wide range of disease processes are not being successfully addressed in clinical trials. We anticipate that broader targeting of more of the underlying mechanisms of Alzheimer’s disease will increase the chances of future drug trials being successful.”

About this news from Alzheimer’s research

Author: press office
Source: Beth Israel Deaconess Medical Center
Contact: Press Office – Beth Israel Deaconess Medical Center
Picture: The image is in the public domain

Original research: Open access.
“Most pathways can be implicated in the pathogenesis of Alzheimer’s disease” by Sarah L. Morgan et al. Frontiers in Neuroscience


abstract

See also

This shows DNA

Most signaling pathways can be implicated in the pathogenesis of Alzheimer’s disease

Alzheimer’s disease (AD) is a complex neurodegenerative disease. The relative contribution of the various underlying functional mechanisms is poorly understood.

To fully understand the context and distribution of signaling pathways that contribute to AD, we performed text mining to produce a comprehensive, systematic assessment of the breadth and diversity of biological signaling pathways within a corpus of 206,324 abstract dementia publications.

A total of 91% (325/335) of the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways have publications that contain an association above at least 5 studies, while 63% of pathway terms have at least 50 studies showing a clear association with AD.

Despite major technological advances, the same high-level signaling pathways have been consistently implicated in AD for 30 years, including ADVERTISEMENT, immune system, metabolic pathways, cholinergic synapse, long-term depression, proteasome, diabetes, Cancerand chemokine signaling. The AD pathways studied appear to be biased: animal model and human studies prioritize different AD pathways.

Surprisingly, human genetic discoveries and drug targeting are not enriched in the most commonly studied signaling pathways.

Our results suggest that not only is this disorder incredibly complex, but its functional reach is nearly global. As a result of our study, the research findings can now be evaluated in the context of the broader AD literature, aiding the design of drug therapies that target a broader range of mechanisms.

The results of this study can be viewed at www.adpathways.org.

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