In the battle against Alzheimer’s disease (AD), scientists have uncovered a hidden army of weakly activated neuroinflammation pathways that act as the core warriors behind chronic neurodegeneration. Similar to how an elite force operates under the radar, these pathways respond to low-level and weakly activated inflammation and hypoxia, gradually leading to the breakdown of the brain. By studying transcriptomics data from two large-scale datasets, researchers identified seven categories of signaling pathways involved in AD, including immune response, x-core signaling, apoptosis, lipid dysfunction, biosynthesis and metabolism, and mineral absorption. Within these pathways, certain key players such as MAPK, Rap1, NF-kappa B, HIF-1, PI3K-Akt, Wnt, TGF-beta, Hippo, and TNF were identified as the leaders of the neuroinflammation army. What’s fascinating is how these pathways not only contribute to inflammation but are also associated with virus infection, highlighting a potential link between viral factors and AD. Further investigation into the detailed signaling cascades of these pathways could potentially unveil novel therapeutic targets for effective AD treatment and prevention. To delve further into this groundbreaking research, check out the full article.

ObjectivesNeuroinflammation signaling has been identified as an important hallmark of Alzheimer’s disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.Materials and methodsFrom a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets and pathways in AD using the two large-scale transcriptomics datasets, i.e., Mayo Clinic (77 controls and 81 AD samples) and ROSMAP (97 controls and 260 AD samples).ResultsOur analysis identified interesting core neuroinflammation signaling pathways, which are not systematically reported in the previous studies of AD. Specifically, we identified 7 categories of signaling pathways implicated on AD and related to virus infection: immune response, x-core signaling, apoptosis, lipid dysfunctional, biosynthesis and metabolism, and mineral absorption signaling pathways. More interestingly, most of the genes in the virus infection, immune response, and x-core signaling pathways are associated with inflammation molecular functions. The x-core signaling pathways were defined as a group of 9 signaling proteins: MAPK, Rap1, NF-kappa B, HIF-1, PI3K-Akt, Wnt, TGF-beta, Hippo, and TNF, which indicated the core neuroinflammation signaling pathways responding to the low-level and weakly activated inflammation and hypoxia and leading to the chronic neurodegeneration. It is interesting to investigate the detailed signaling cascades of these weakly activated neuroinflammation signaling pathways causing neurodegeneration in a chronic process, and consequently uncover novel therapeutic targets for effective AD treatment and prevention.ConclusionsThe potential core neuroinflammation and associated signaling targets and pathways were identified using integrative network analysis on two large-scale transcriptomics datasets of AD.

Read Full Article (External Site)