Abstract: Of the 341 known biological pathways, 91% were associated with Alzheimer’s disease.
Source: Beth Israel Deaconess Medical Center
Nearly 6 million seniors have Alzheimer’s disease in the United States, and the number 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 anxiety that deprives people of their ability to live independently.
Currently, the biological mechanisms underlying Alzheimer’s disease are poorly understood; as a result, there are few effective treatments and there is no cure for the disease.
In a recent study, a research team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) conducted a systematic evaluation of more than 200,000 scientific publications to understand the breadth and diversity of biological pathways – key molecular chain reactions that drive cell changes – that contribute to Alzheimer’s disease. research in the last 30 years.
The team found that although almost all known pathways are disease-related, the most commonly associated biological mechanisms — including those related to the immune system, metabolism, and long-term depression — have not changed significantly in 30 years, despite major technological advances.
The work of scientists, published in Limits in the aging of neurosciencewill advance research into the mechanisms of neurodegeneration.
“The burden of Alzheimer’s disease is constantly growing, leading us to a neurological epidemic,” said Dr. Winston A. Hide, director of the Precision RNA Medicine Core Facility at BIDMC and associate professor of medicine at Harvard Medical School.
“Our findings suggest that not only is this disorder incredibly complex, but that its pathology involves most of the known biological pathways. This means that the effects of the disease are far broader in the body than we thought. ”
The team conducted an exhaustive textual search of 206,324 summaries of pathway-specific dementia publications published since 1990. They then looked at 341 known biological pathways and determined how many publications link a particular pathway to the disease.
Researchers found that 91 percent of the pathways – all but seven – were linked to Alzheimer’s disease. Nearly half of the pathways have been linked to Alzheimer’s disease in more than 100 scientific papers.
They also found that the first 30 pathways most frequently mentioned in the literature remained relatively consistent over the past 30 years suggesting that most disease studies focused on a small subset of 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 this study and now a lecturer at Queen Mary University in London.
“Given the unexpected diversity of pathways associated with Alzheimer’s disease, a wide range of diseases have not been successfully targeted in clinical trials. We hypothesize that comprehensive targeting of multiple related underlying mechanisms in Alzheimer’s disease will increase the chances of success in future drug trials. ”
About this news about Alzheimer’s disease research
Original research: Open access.
“Most pathways may be associated with the pathogenesis of Alzheimer’s disease”Sarah L. Morgan et al. Limits in neuroscience
Most pathways may be associated with the pathogenesis of Alzheimer’s disease
Alzheimer’s disease (AD) is a complex neurodegenerative disorder. The relative contribution of a number of fundamental functional mechanisms is poorly understood.
To comprehensively understand the context and distribution of pathways that contribute to AD, we performed text mining to generate a comprehensive, systematic assessment of the breadth and diversity of biological pathways within a corpus of 206,324 abstracts of publications on dementia.
A total of 91% (325/335) of the routes from the Kyoto Encyclopedia of Genes and Genomes (KEGG) have publications containing associations over it at least 5 studies, while 63% of path terms have at least 50 studies that provide a clear association with AD.
Despite great technological advances, the same set of top-ranked pathways has been consistently associated with AD for 30 years, including AD,, immune system,, metabolic pathways,, cholinergic synapse,, prolonged depression,, proteasome,, diabetes,, Cancerand chemokine signaling. The AD pathways studied seem biased: studies on animal models and human subjects give priority to different AD pathways.
Surprisingly, human genetic discoveries and drug targeting have not been enriched by the most commonly studied pathways.
Our findings suggest that not only is this disorder incredibly complex, but that its functional reach is also almost global. As a consequence of our study, the results of the research can now be assessed in the context of the broader literature on AD, 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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