ArticlePLoS biology2024
Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer's disease.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Machine Learning and Multimodal Biomarker Discovery in Alzheimer's Disease.Brain sciences · 2026Review
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Unveiling the molecular mechanism of Qingwen Baidu decoction against dengue fever: an integrated study of bioinformatic analysis, machine learning and network pharmacology.Functional & integrative genomics · 2026Article
- Microglia-driven neuroinflammatory signaling in neurodegeneration: mechanisms and therapeutic opportunities.Molecular biology reports · 2026Review
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- A diagnostic plasma omics-biomarker for Alzheimer's disease informed by microglial single-cell transcriptomics: A pilot study.bioRxiv : the preprint server for biology · 2026Article
- Integrating polygenic and transcriptional risk scores for detecting Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.Cell reports · 2026Article
- A Meta-analysis to Identify Common Key Genes Across Ageing, Alzheimer's and Parkinson's Diseases.Annals of neurosciences · 2026Article
- Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Balanced deep learning on multi-omics networks identifies molecular subgroups of pathological brain aging.medRxiv : the preprint server for health sciences · 2026Article
- Optimization of potential targets for antidepressant Chinese medicines: AI and multi-omics methods.Chinese medicine · 2026Review
- Decoding Alzheimer's Disease One Cell Class at a Time.Cellular and molecular neurobiology · 2026Review
- Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.Molecular diversity · 2026Review
- Exposome influences: a multi-omics perspective on the combined toxic effects of pharmaceuticals and personal care products in Alzheimer's disease.Frontiers in toxicology · 2026Review
- Computational whole-body-exposome models for global precision brain health.Nature communications · 2025Article
- Toward a Unified Framework in Molecular Neurobiology of Alzheimer's Disease: Revisiting the Pathophysiological Hypotheses.Molecular neurobiology · 2025Review
- Systematic Review: Proteomics-Driven Multi-Omics Integration for Alzheimer's Disease Pathology and Precision Medicine.Neurology international · 2025Review
- Integrating imaging and omics for enhanced subtyping of mild cognitive impairment associated with Alzheimer's disease.Journal of translational medicine · 2025Article
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, phagosome, and mTOR signaling pathways altered in AD early and late stages. AD cross-omics data integration with transcriptomic data from an SNCA mouse model revealed an overlapping signature. Furthermore, we leveraged single-nuclei RNA-seq data to identify distinct cell-types that most likely mediate molecular profiles. Lastly, we identified that the multimodal clusters uncovered cerebrospinal fluid biomarkers poised to monitor AD progression and possibly cognition. Our cross-omics analyses provide novel critical molecular insights into AD.
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