Overview: Of the 341 known biological pathways, 91% are linked to Alzheimer’s disease.
Source: Beth Israel Diaconess Medical Center
Nearly 6 million older adults have Alzheimer’s disease in the United States, a number expected to double by 2050.
Already the sixth leading cause of death, Alzheimer’s is a complex neurodegenerative disease that causes memory loss, confusion, poor judgment, depression, delusions and agitation that rob 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 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 review of more than 200,000 scientific publications to understand the breadth and diversity of biological pathways — important molecular chain reactions that cause changes in cells. — who have contributed to Alzheimer’s disease through research over the past 30 years.
The team found that while nearly all known pathways have been linked to the disease, the most 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 the scientists, published in Frontiers in aging neurosciencewill advance research into the mechanisms of neurodegeneration.
“The burden of Alzheimer’s disease is steadily increasing, driving us towards 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 findings suggest that not only is this condition incredibly complex, but its pathology encompasses most of the known biological pathways. This means that the effects of the disease are much broader in the body than we realized.”
The team conducted an in-depth text search of 206,324 disease pathway publication excerpts that have been published since 1990. They then looked at 341 known biological pathways and determined how many publications linked a particular pathway to the disease.
The researchers found that 91 percent of the pathways — all but seven — were linked to Alzheimer’s disease. Nearly half of the pathways were linked to Alzheimer’s disease in more than 100 scientific papers.
They also found that the 30 major pathways most frequently referenced in the literature remained relatively consistent over the past 30 years, suggesting that most studies of the disease have focused on a small subset of all known disease-related pathways.
“Clinical studies aimed at slowing the onset or slowing the progression of Alzheimer’s disease have largely failed,” said first author Sarah Morgan, a postdoctoral researcher at BIDMC during the scope of this study and now a lecturer at the Queen Mary University of London.
“Given that an unexpected diversity of pathways is associated with Alzheimer’s disease, a wide variety of disease processes are not being successfully addressed in clinical trials. We hypothesize that fully targeting more of the associated underlying mechanisms in Alzheimer’s disease will increase the chances of success in future drug trials.”
About this research news on Alzheimer’s disease
Original research: Open access.
†Most pathways may be related to the pathogenesis of Alzheimer’s diseaseby Sarah L. Morgan et al. Frontiers in neuroscience
Most pathways may be related to the pathogenesis of Alzheimer’s disease
Alzheimer’s disease (AD) is a complex neurodegenerative disorder. The relative contribution of the numerous underlying functional mechanisms is poorly understood.
To fully understand the context and distribution of pathways contributing to AD, we performed text-mining to generate an exhaustive, systematic assessment of the breadth and diversity of biological pathways across a corpus of 206,324 publications on dementia.
A total of 91% (325/335) of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways have publications associated with through at least 5 studies, while 63% of trajectory terms have at least 50 studies that have a clear association with AD.
Despite major advances in technology, the same set of top-ranked paths has been consistently related to AD for 30 years, including: ADVERTISEMENT† immune system† metabolic pathways† cholinergic synapse† prolonged depression† proteasome† diabetes mellitus† cancerand chemokine signaling† The AD pathways studied appear biased: studies in animal models and humans prioritize different AD pathways.
Surprisingly, human genetic discoveries and drug targeting are not enriched in the most studied pathways.
Our findings suggest that not only is this condition incredibly complex, but its functional range is nearly global. As a result of our study, research findings can now be assessed in the context of the broader AD literature, supporting the design of drug therapies targeting a wider range of mechanisms.
The results of this research can be found at: www.adpathways.org†
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