Almost every known biological pathway in the brain is linked to Alzheimer’s disease

Nearly six million older adults 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, impaired 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 while 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. changed significantly in 30 years, despite significant technological changes. advances. The work of scientists, published in Frontiers of the neurosciences of agingwill advance research on the mechanisms of neurodegeneration and can be explored at

The burden of Alzheimer’s disease continues to grow, dragging us towards a neurological epidemic. 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 wider in the body than we thought.”

Winston A. Hide, PhD, Director of the Central Precision RNA Medicine Platform at BIDMC and Associate Professor of Medicine at Harvard Medical School

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 comprehensively targeting more mechanisms under diseases associated with Alzheimer’s disease will increase the chances of success in future drug trials.

Co-authors included Pourya Naderi, Yered Pita-Juarez and Ioannis S. Vlachos of BIDMC; Katjusa Koler from the University of Sheffield; Lars Bertram from the University of Lubeck and Dmitri Prokopenko and Rudolph Tanzi from Massachusetts General Hospital and Harvard Medical School.

This work was supported in part by the Cure Alzheimer Fund.


Journal reference:

Morgan, SL, et al. (2022) Most of the pathways can be linked to the pathogenesis of Alzheimer’s disease. Frontiers of the neurosciences of aging.

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