An Integrated Molecular Atlas of Alzheimer’s Disease

Abstract

INTRODUCTION: Embedding single-omics disease associations into the wider context of multi-level molecular changes in Alzheimer's disease (AD) remains one central challenge in AD research. METHODS: Results from numerous AD-specific omics studies from AMP-AD, NIAGADS, and other initiatives were integrated into a comprehensive network resource and complemented with molecular associations from large-scale population-based studies to provide a global view on AD. RESULTS: We present the AD Atlas, an online resource (www.adatlas.org) integrating over 20 large studies providing disease-relevant information on 20,353 protein-coding genes, 8,615 proteins, 997 metabolites and 31 AD-related phenotypes. Multiple showcases demonstrate the utility of this resource for contextualization of AD research results and subsequent downstream analyses, such as drug repositioning approaches. DISCUSSION: By providing a global view on multi-omics results through a user-friendly interface, the AD Atlas enables the formulation of molecular hypotheses and retrieval of clinically relevant insights that can be validated in follow-up analyses or experiments.

Integration of proteomics and metabolomics – insights into inflammation, metabolic dysregulation, and vascular aspects in AD

“…We further investigated potential gene co-expression of CSF proteins and above-described lipid mediators -regulating genes using AD Atlas [26] and seven brain regions. Strong associations were observed within investigated proteins, however no associations were observed between those proteins and lipid mediators enzymatic regulators.…”

“…Network parameters: Tissue – brain cerebrum; tissue type – normal tissue; maximal number of connections pre gene – 25. Additional co-expression data from seven brain regions [25] and genetic associations between input proteins and AD were obtained using the AD Atlas [26]. The list of proteins submitted to the network analyses is provided in Table S2 .…”

The Alzheimer's Cell Atlas (TACA): A single‐cell molecular map for translational therapeutics accelerator in Alzheimer's disease

“…To date, several useful bioinformatics tools have been developed for a broader range of sc/sn data set exploration, such as Single Cell Portal ( https://singlecell.broadinstitute.org/single_cell ) and CELLxGENE ( https://cellxgene.cziscience.com/ ), and for AD studies, such as Agora ( https://agora.adknowledgeportal.org/genes ) and the Alzheimer's Disease Atlas ( https://adatlas.helmholtz‐muenchen.de/ ). 46 We envision that it would be beneficial to the AD research community if TACA could establish collaborative work with these resources in the future. For example, a pipeline may be implemented to automatically import the annotated AD sc/sn data sets from Single Cell Portal, and our analysis pipeline will conduct analyses such as DE, CCI, and drug screening.…”

Effects of a ketogenic and low‐fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease

“…Cholesterol metabolism is consistently reported to be dysregulated in AD and AD-related diseases. [20][21][22] Cholesterol accumulation in the brain contributes to hepatic encephalopathy, a chronic liver disease that leads to neuron loss and increased risk for AD, through bile acid-mediated effects on the farnesoid X receptor. 23 This observation is significant because bile acids, the main source of cholesterol elimination in the brain, are transformed by the gut microbiota.…”