The critical molecular biological pathways that drive changes in cells – that contribute to Alzheimer’s disease have been revealed by scientists.
The team found that, while nearly all known pathways have been linked to the disease, the most frequently associated biological mechanisms – including those related to the immune system, metabolism and long-term depression -have not significantly changed in 30 years, despite major technological advances. The scientists’ work was published in Frontiers in Aging Neuroscience.
Alzheimer’s Disease Statistics
Nearly six 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 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.
‘Alzheimer’s disease is not only incredibly complex, but its pathology includes most known biological pathways. This means that the diseases effects are far broader in the body than we realized.
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“The burden of Alzheimer’s disease is steadily increasing, driving us towards a neurological epidemic,” said Winston A. Hide, PhD, director of the Precision RNA medicine Core Facility at BIDMC and an associate professor of medicine at Harvard Medical School.
The team performed an exhaustive text search of 206,324 pathway-specific dementia publication abstracts published since 1990. Next, they looked at 341 known biological pathways and determined how many publications linked a given pathway to the disease.
Pathways in Alzheimer’s Disease
The researchers found that 91% of 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.
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They also found that the top-ranked 30 pathways most frequently referred to in literature remained relatively consistent over the last 30 years, suggesting that most studies of the disease have focused on a small subset of all the known disease-associated pathways.
“Clinical trials aiming to either delay the onset or slow the progression of Alzheimer’s disease have largely failed,” said study first author Sarah Morgan, a postdoctoral researcher at BIDMC during the extent of this research and now a lecturer at Queen Mary University of London.
“Given that an unexpected diversity of pathways is 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 of the associated underlying mechanisms in Alzheimer’s disease will increase the chances of success in future drug trials.”
Source: Eurekalert
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