Summary: Of 341 known biological pathways, 91% are linked to Alzheimer’s disease.
Source: Beth Israel Deaconess Medical Center
Nearly 6 million seniors have Alzheimer’s disease in the United States, a number that is 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 restlessness that robs people of their ability to live. independently.
Currently, the biological mechanisms underlying Alzheimer’s disease are poorly understood; therefore, 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 pathways – from chain reactions key molecules that lead to changes in cells – which contribute to Alzheimer’s disease by research of the past 30 years.
The team found that although nearly every known pathway has been linked to disease, the most frequently associated biological mechanisms, including those related to the immune system, metabolism and long-term depression, have not. not changed significantly in 30 years, despite major technological advances. advances.
The work of scientists, published in Frontiers of the neurosciences of agingwill advance research on the mechanisms of neurodegeneration.
“The burden of Alzheimer’s disease continues to rise, driving us toward a neurological epidemic,” said Winston A. Hide, Ph.D., director of the Precision RNA medicine Core Facility at BIDMC and associate professor of medicine at Harvard Medical School.
“Our results suggest that not only is this disorder incredibly complex, but that its pathology includes most of the known biological pathways. This means that the effects of the disease are much more widespread in the body than we thought.
The team performed a comprehensive text search of 206,324 abstracts of pathway-specific dementia publications published since 1990. Next, they examined 341 known biological pathways and determined the number of publications related to a given disease pathway.
The researchers found that 91% of the pathways, all but seven, were linked to Alzheimer’s disease. Almost half of the pathways were linked to Alzheimer’s disease in more than 100 scientific papers.
They also found that the top 30 most frequently 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 the disease. all known pathways associated with the disease.
“Clinical trials aimed at delaying the onset or slowing the progression of Alzheimer’s disease have largely failed,” said study first author Sarah Morgan, a postdoctoral researcher at BIDMC during the time of this research and now a lecturer at Queen Mary University of London.
“Because an unexpected diversity of pathways are associated with Alzheimer’s disease, a wide range of disease processes are not being successfully targeted in clinical trials. We hypothesize that comprehensive targeting of more of the underlying mechanisms associated with Alzheimer’s disease will increase the chances of success in future drug trials.
About this Alzheimer’s disease research news
Author: Press office
Source: Beth Israel Deaconess Medical Center
Contact: Press Office – Beth Israel Deaconess Medical Center
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Original research: Free access.
“Most pathways can be linked to the pathogenesis of Alzheimer’s disease” by Sarah L. Morgan et al. Frontiers in Neuroscience
Summary
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Most pathways can be linked to the pathogenesis of Alzheimer’s disease
Alzheimer’s disease (AD) is a complex neurodegenerative disease. The relative contribution of the many underlying functional mechanisms is poorly understood.
To fully understand the context and distribution of pathways that contribute to AD, we performed text mining to generate a comprehensive and systematic assessment of the extent and diversity of biological pathways in a corpus of 206,324 publication abstracts. on dementia.
A total of 91% (325/335) of the routes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) have publications containing an association Going through at least 5 studies, while 63% of pathway terms have at least 50 studies providing a clear association with AD.
Despite major advances in technology, the same set of top-ranked pathways have been consistently linked to AD for 30 years, including AD, immune system, metabolic pathways, cholinergic synapse, long term depression, proteasome, Diabetes, cancerand chemokine signaling. The studied AD pathways seem to be biased: studies on animal models and on human subjects favor different AD pathways.
Surprisingly, human genetic discovery and drug targeting are not enriched in the most frequently studied pathways.
Our findings suggest that not only is this disorder incredibly complex, but its functional reach is also nearly global. As a result of our study, the research findings can now be evaluated in the context of the broader AD literature, supporting the design of drug therapies that target a wider range of mechanisms.
The results of this study can be explored at www.adpathways.org.
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