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

Abstract

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.

Role of non‑coding RNAs as biomarkers and the application of omics technologies in Alzheimer's disease (Review)

“…The importance and value of omics and ncRNAs are highlighted through the process of the development of personalized diagnostic and therapeutic tools. For this purpose, various studies have focused on novel pathways and networks, demonstrating novel pathological mechanisms related to AD and linked to other diseases (29)(30)(31). The present review aimed to summarize the current evidence on the role and utilization of ncRNAs as biomarkers in AD, as well as to describe the application of omics technologies and large-scale data in the efficient prediction, diagnosis and treatment of AD.…”

Transcriptomic signatures of Aβ- and tau-induced neuronal dysfunction reveal inflammatory processes at the core of Alzheimer’s disease pathophysiology

“…Despite the moderate isolated influence of single molecules, multifactorial and complex disorders like AD are more recently approached in terms of comprehensive biological processes expressing the disease’s signatures (Calabrò et al, 2021; Iturria-Medina et al, 2022; Morgan et al, 2022). We proceeded to compare the three neuronal activity alterations-associated gene sets to ontology terms from various sources in Metascape (Zhou et al, 2019), detecting the molecular pathways that are significantly overrepresented in the combination of such genetic signatures ( Methods, Statistical Analyses, Supplementary File 3).…”

“…Alzheimer’s disease (AD) seems to be determined by multiple interacting molecular elements and generalized dysfunction (Calabrò et al, 2021; Iturria-Medina et al, 2022). Notably, 91% of all molecular pathways recorded in the Kyoto Encyclopedia of Genes and Genomes (KEGG) have been found to be associated with AD in at least 5 studies (Morgan et al, 2022). In cell culture, animal and post-mortem research, mechanisms of neuroinflammation/immune system, metabolism, cholinergic synapse, cancer, diabetes and chemokine signaling typically rank high in associations with AD (Calabrò et al, 2021; Morgan et al, 2022; Santiago & Potashkin, 2021).…”

“…Notably, 91% of all molecular pathways recorded in the Kyoto Encyclopedia of Genes and Genomes (KEGG) have been found to be associated with AD in at least 5 studies (Morgan et al, 2022). In cell culture, animal and post-mortem research, mechanisms of neuroinflammation/immune system, metabolism, cholinergic synapse, cancer, diabetes and chemokine signaling typically rank high in associations with AD (Calabrò et al, 2021; Morgan et al, 2022; Santiago & Potashkin, 2021). However, these results may not fully capture disease progression in the living human organism.…”

Extracellular Vesicles, Cell-Penetrating Peptides and miRNAs as Future Novel Therapeutic Interventions for Parkinson’s and Alzheimer’s Disease

“…Taking a closer look at both AD and PD suggests many commonalities in their pathophysiology, with many genes shared and co-expressed [ 32 ], as well as stark differences [ 33 ]. AD is well known for its increased concentration of Aβ42 (β-amyloid 42—due to mutations in the APP gene) which encourages the production of oligomers (that are neurotoxic).…”