AUTHOR=Morgan Sarah L. , Naderi Pourya , Koler Katjuša , Pita-Juarez Yered , Prokopenko Dmitry , Vlachos Ioannis S. , Tanzi Rudolph E. , Bertram Lars , Hide Winston A. 

TITLE=Most Pathways Can Be Related to the Pathogenesis of Alzheimer’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.846902

DOI=10.3389/fnagi.2022.846902

ISSN=1663-4365

ABSTRACT=<p>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 <italic>via</italic> 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 <italic>AD</italic>, <italic>immune system</italic>, <italic>metabolic pathways</italic>, <italic>cholinergic synapse</italic>, <italic>long-term depression</italic>, <italic>proteasome</italic>, <italic>diabetes</italic>, <italic>cancer</italic>, and <italic>chemokine signaling</italic>. 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 <ext-link ext-link-type="uri" xlink:href="http://www.adpathways.org" xmlns:xlink="http://www.w3.org/1999/xlink">www.adpathways.org</ext-link>.</p>