Bharthur Sanjay, ApoorvaPatania, AliceYan, XiaoranSvaldi, DianaDuran, TugceShah, NirajNemes, SaraChen, EricApostolova, Liana G.2023-11-292023-11-292022Bharthur Sanjay A, Patania A, Yan X, et al. Characterization of gene expression patterns in mild cognitive impairment using a transcriptomics approach and neuroimaging endophenotypes. Alzheimers Dement. 2022;18(12):2493-2508. doi:10.1002/alz.12587https://hdl.handle.net/1805/37230Introduction: Identification of novel therapeutics and risk assessment in early stages of Alzheimer's disease (AD) is a crucial aspect of addressing this complex disease. We characterized gene-expression patterns at the mild cognitive impairment (MCI) stage to identify critical mRNA measures and gene clusters associated with AD pathogenesis. Methods: We used a transcriptomics approach, integrating magnetic resonance imaging (MRI) and peripheral blood-based gene expression data using persistent homology (PH) followed by kernel-based clustering. Results: We identified three clusters of genes significantly associated with diagnosis of amnestic MCI. The biological processes associated with each cluster were mitochondrial function, NF-kB signaling, and apoptosis. Cluster-level associations with cortical thickness displayed canonical AD-like patterns. Driver genes from clusters were also validated in an external dataset for prediction of amyloidosis and clinical diagnosis. Discussion: We found a disease-relevant transcriptomic signature sensitive to prodromal AD and identified a subset of potential therapeutic targets associated with AD pathogenesis.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalAlzheimer's diseaseNF-kB signalingApoptosisCell proliferationCortical thicknessGene expressionImaging geneticsRisk genesArticle