‘Alzheimer’s Overlaps with Many Paths’

Published on June 24, 2022

Alzheimer’s disease, a complex neurological disorder, shares a surprising number of pathways with various biological processes. Using text-mining techniques, researchers analyzed over 200,000 publication abstracts related to dementia to identify the pathways associated with Alzheimer’s. They found that 91% of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were linked to the disease in at least 5 studies, while 63% of pathway terms had strong associations with Alzheimer’s based on at least 50 studies. Astonishingly, these same pathways have consistently been implicated in Alzheimer’s for three decades. The pathways include immune system responses, metabolism, cholinergic synapse activity, and more. Interestingly, animal model studies tend to focus on different pathways than human subject studies. Strikingly, the most frequently studied pathways are not enriched in human genetic discoveries or drug targeting efforts. The study’s findings provide a comprehensive understanding of the wide-ranging effects of Alzheimer’s and suggest that future drug therapies should consider targeting a broader set of mechanisms. To explore the research further, visit www.adpathways.org.

Alzheimer’s disease (AD) is a complex neurodegenerative disorder. The relative contribution of the numerous underlying functional mechanisms is poorly understood. To comprehensively understand the context and distribution of pathways that contribute to AD, we performed text-mining to generate an exhaustive, systematic assessment of the breadth and diversity of biological pathways within a corpus of 206,324 dementia publication abstracts. A total of 91% (325/335) of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways have publications containing an association via at least 5 studies, while 63% of pathway terms have at least 50 studies providing a clear association with AD. Despite major technological advances, the same set of top-ranked pathways have been consistently related to AD for 30 years, including AD, immune system, metabolic pathways, cholinergic synapse, long-term depression, proteasome, diabetes, cancer, and chemokine signaling. AD pathways studied appear biased: animal model and human subject studies prioritize different AD pathways. Surprisingly, human genetic discoveries and drug targeting are not enriched in the most frequently studied pathways. Our findings suggest that not only is this disorder incredibly complex, but that its functional reach is also nearly global. As a consequence of our study, research results can now be assessed in the context of the wider AD literature, supporting the design of drug therapies that target a broader range of mechanisms. The results of this study can be explored at www.adpathways.org.

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