ArticleNeuron2021
Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer's Disease.
Open access · bronzeAbstract read
In one paragraph
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 2 pooled it
13.0field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
126 citing papers in PubMed, 2 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- Multi-omics and high-spatial-resolution omics: deciphering complexity in neurological disorders.GigaScience · 2025Pooled it
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Article
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Astrocytic lactate shuttle disruption and the energy-starved lysosome in Alzheimer's disease.Research square · 2026Article
- Dysregulation of the TFEB-ATP6V0C axis in microglia exacerbates α-synuclein pathology through impaired lysosomal acidification in Parkinson's disease.Cell death and differentiation · 2026Article
- Targeting lysosomal pH restores mitochondrial quality control in GBA1-mutant Parkinson's disease.Translational neurodegeneration · 2026Article
- An electrophysiological and proteomics roadmap for human induced glutamatergic neurons: fine-tuning of culture conditions for pathophysiological studies.Cell death discovery · 2026Article
- Allele specific expression in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Single-cell transcriptomic analysis reveals APOE genotype-dependent sex differences in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo.Nature neuroscience · 2026Article
- 3D genetic architecture of schizophrenia risk across three neuronal subtypes.Molecular psychiatry · 2026Article
- Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model.Experimental & molecular medicine · 2026Article
- Leveraging machine learning and network biology approaches to predict brain gene expression from blood transcriptomes.GigaScience · 2026Article
- Functional implications of polygenic risk for schizophrenia in human neurons.Nature communications · 2026Article
- APP Deficiency Ameliorates FAD Presenilin 1 F105C and A246E Mutations-induced Mitochondrial Dysfunction in Human Cortical Neurons.International journal of biological sciences · 2026Article
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- A study of gene expression in the living human brain.Molecular psychiatry · 2026Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
42 authors at 8 institutions in 2 countries.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Aiqun LiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Michiko SekiyaDepartment of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan; Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Noam D BeckmannDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Xiuming QuanDepartment of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Nadine SchrodeIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Michael B FernandoIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Alex YuIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Li ZhuDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Neurology, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Jiqing CaoDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Neurology, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Liwei LyuIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Emrin HorgusluogluDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Qian WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Lei GuoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Yuan-Shuo WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Ryan NeffDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Won-Min SongDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Erming WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Qi ShenDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Xianxiao ZhouDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Chen MingDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Seok-Man HoIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Sezen VatanseverDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
H Ümit KaniskanDepartment of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jian JinDepartment of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ming-Ming ZhouDepartment of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Kanae AndoDepartment of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
Lap HoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Paul A SlesingerNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Zhenyu YueDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jun ZhuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Pavel KatselDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Psychiatry, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Sam GandyDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michelle E EhrlichDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Valentina FossatiThe New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
Scott NoggleThe New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
Dongming CaiDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Neurology, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Vahram HaroutunianNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Psychiatry, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Koichi M IijimaDepartment of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan; Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Eric SchadtDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Kristen J BrennandIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: bin.zhang@mssm.edu.
Icahn School of Medicine at Mount Sinai · USAllen Institute for Brain Science · USJames J. Peters VA Medical Center · USNagoya City University · JPNew York Stem Cell Foundation · USThe King's College · USNational Center for Geriatrics and Gerontology · JPTokyo Metropolitan University · JP
Funding
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0MIntegrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0MOmics-Based Predictive Modeling of Age-Dependent Outcome to Influenza InfectionU01AI111598 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GHEDIN, ELODIE · 2013 to 2017
$13.3MIntegrative Network Modeling of Cognitive Resilience to Alzheimer's DiseaseR01AG057907 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, HAROUTUNIAN, VAHRAM · 2017 to 2021
$6.3MValidation of Antibody Reagents for 15 High Priority AMP-AD TargetsRF1AG057443 · NIA · SAGE BIONETWORKS · PI BRENNAN , PAUL, MANGRAVITE, LARA M · 2017 to 2019
$6.0MGenomic approach to identification of microglial networks involved in Alzheimer’s disease riskU01AG058635 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GOATE, ALISON M · 2018 to 2022
$4.8MSystems modeling of shared and distinct molecular mechanisms underlying comorbid Major Depressive Disorder and Alzheimer's diseaseR01AG062355 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, SALTON, STEPHEN R · 2018 to 2022
$4.7MIdentification and characterization of AD risk networks using multi-dimensional "omics" dataU01AG052411 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2016 to 2020
$4.5MCell-type-specific NRXN1alpha alternative splicing changes in psychiatric diseaseR01MH121074 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER, FANG, GANG · 2019 to 2023
$4.4MNovel Network Biology Approaches to Reposition FDA-approved Drugs for Alzheimer's DiseaseR01AG068030 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER, CAI, DONGMING · 2020 to 2024
$4.2MMolecular Characterization and Validation of Gender Differences in Alzheimers Disease PathogenesisRF1AG054014 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CAI, DONGMING, ZHANG, BIN · 2016 to 2016
$4.2MTranscriptional Control of Neuroinflammation in Alzheimer's DiseaseR01AG072562 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CAI, DONGMING, ZHOU, MING-MING · 2021 to 2025
$4.2MBLRD VA I01 BX003380NIAID NIH HHS U01 AI111598NIA NIH HHS P30 AG066514NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG062355NIA NIH HHS R01 AG068030NIA NIH HHS R01 AG072562NIA NIH HHS R56 AG058655NIA NIH HHS RF1 AG044546NIA NIH HHS RF1 AG048923NIA NIH HHS RF1 AG054014NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057443NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG059319NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG058635NIDA NIH HHS R01 DA043247NIDCR NIH HHS R03 DE026814NIDDK NIH HHS R01 DK118243NIMH NIH HHS R01 MH121074NIMH NIH HHS R56 MH101454RRD VA I01 RX002290
Abstract
To identify the molecular mechanisms and novel therapeutic targets of late-onset Alzheimer's Disease (LOAD), we performed an integrative network analysis of multi-omics profiling of four cortical areas across 364 donors with varying cognitive and neuropathological phenotypes. Our analyses revealed thousands of molecular changes and uncovered neuronal gene subnetworks as the most dysregulated in LOAD. ATP6V1A was identified as a key regulator of a top-ranked neuronal subnetwork, and its role in disease-related processes was evaluated through CRISPR-based manipulation in human induced pluripotent stem cell-derived neurons and RNAi-based knockdown in Drosophila models. Neuronal impairment and neurodegeneration caused by ATP6V1A deficit were improved by a repositioned compound, NCH-51. This study provides not only a global landscape but also detailed signaling circuits of complex molecular interactions in key brain regions affected by LOAD, and the resulting network models will serve as a blueprint for developing next-generation therapeutic agents against LOAD.
Indexed as
Databases, GeneticAlzheimer DiseaseAnimalsAnimals, Genetically ModifiedBrainDrosophila melanogasterFemaleGene Regulatory NetworksHumansInduced Pluripotent Stem CellsMaleSequence Analysis, RNASignal TransductionAlzheimer’s diseaseATP6V1ADrosophilahuman induced pluripotent stem cellNCH-51network biologyneuronal dysregulationNGN2 neuronsomics
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