Characterization of gene expression patterns in mild cognitive impairment using a transcriptomics approach and neuroimaging endophenotypes

Abstract

Introduction: 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.

Hydroxytyrosol Alleviates Obesity-Induced Cognitive Decline by Modulating the Expression Levels of Brain-Derived Neurotrophic Factors and Inflammatory Factors in Mice

“…Western blot was conducted as described previously with some modifications . First, the protein of brain tissue was extracted using a mixture of lysis solution and protease inhibitor.…”

“…Western blot was conducted as described previously with some modifications. 34 First, the protein of brain tissue was extracted using a mixture of lysis solution and protease inhibitor. Next, total protein lysates were separated on 5× SDS-PAGE and electro-blotted onto PVDF membrane, immersed in 5% nonfat milk, sealed for 1.5 h, then cleaned four times with TBST buffer solution.…”