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INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA‐sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co‐expression network analysis (WGCNA) and deconvolution analysis identified AD‐associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD‐associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell‐type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. Highlights: We comprehensively analyze the blood transcriptomes of a well‐characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease.Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers.Immune‐associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Cell growth is orchestrated by a number of interlinking cellular processes. Components of the TOR pathway have been proposed as potential regulators of cell growth, but little is known about their immediate effects on protein synthesis in response to TOR‐dependent growth inhibition. Here, we present a resource providing an in‐depth characterisation of Schizosaccharomyces pombe phosphoproteome in relation to changes observed in global cellular protein synthesis upon TOR inhibition. We find that after TOR inhibition, the rate of protein synthesis is rapidly reduced and that notable phosphorylation changes are observed in proteins involved in a range of cellular processes. We show that this reduction in protein synthesis rates upon TOR inhibition is not dependent on S6K activity, but is partially dependent on the S. pombe homologue of eIF4G, Tif471. Our study demonstrates the impact of TOR‐dependent phospho‐regulation on the rate of protein synthesis and establishes a foundational resource for further investigation of additional TOR‐regulated targets both in fission yeast and other eukaryotes. SYNOPSIS: Serine/threonine protein kinase TOR is a regulator of eukaryotic growth, yet how TOR‐regulated pathways modulate protein synthesis‐related growth processes is unclear. Phosphoproteomic analysis of Schizosaccharomyces pombe reveals a network of interacting proteins exhibiting rapid TOR‐dependent phosphorylation changes potentially regulating protein synthesis. TOR inhibition leads to a rapid reduction in rates of protein synthesis.TOR‐dependent changes in phosphorylation kinetics are observed in a subset of proteins potentially regulating protein synthesis.Tif471, a homologue of eIF4G and downstream target of TOR‐signaling, is one of the mediators of protein synthesis regulation in fission yeast. [ABSTRACT FROM AUTHOR]