ArticleCell reports2024
Spatial transcriptomic patterns underlying amyloid-β and tau pathology are associated with cognitive dysfunction in Alzheimer's disease.
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Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
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24 citing papers in PubMed, 21 citations in OpenAlex.
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- Application of the Allen Human Brain Atlas in Alzheimer's disease and Parkinson's disease.Translational neurodegeneration · 2026Review
- Hierarchical organization of tau topography across the Alzheimer's disease continuum integrates amyloid, connectome, and intrinsic molecular vulnerability.Communications biology · 2026Article
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Gene-Modulated Network Diffusion for Improved Modeling of Amyloid-bioRxiv : the preprint server for biology · 2026Article
- Targeting the astrocyte-microglia EFEMP1-GALNT10 axis: a spatially programmable therapeutic strategy for hippocampal vulnerability in Alzheimer's disease.Journal of translational medicine · 2026Article
- Brain network dynamics determine tau presence while regional vulnerability governs tau load in Alzheimer's disease.Research square · 2026Article
- Mapping individual molecular connectomes in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Whole blood gene expression moderates associations between AD biomarkers and cognitive decline in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuroimaging Epicenters as Vulnerable Nodes in Plasma p-tau217/Aβ42-Positive Alzheimer's Disease.Research (Washington, D.C.) · 2026Article
- A spatially informed matrix normal model for gene co-expression analysis in spatial transcriptomics studies.Nucleic acids research · 2025Article
- Patient-specific functional brain architecture explains cortical patterns of tau PET in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Plasma proteomic Alzheimer's risk score: Biological age clock and pseudotime trajectory.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Synaptic vulnerability to amyloid-β and tau pathologies differentially disrupts emotional and memory neural circuits.Molecular psychiatry · 2025Article
- Brain tissue electrical conductivity as a promising biomarker for dementia assessment using MRI.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Spatial Omics in Clinical Research: A Comprehensive Review of Technologies and Guidelines for Applications.International journal of molecular sciences · 2025Review
- Article
- Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases.Genes · 2025Review
- Spatial transcriptomics reveals an unexpected impact of tau and tau pathology on the expression of transthyretin.Frontiers in aging neuroscience · 2025Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Meichen YuIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Network Science Institute, Bloomington, IN, USA. Electronic address: meiyu@iu.edu.
Shannon L RisacherIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Kwangsik T NhoIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Network Science Institute, Bloomington, IN, USA.
Qiuting WenIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Adrian L OblakCenter for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Frederick W UnverzagtIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
Liana G ApostolovaIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Martin R FarlowIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Jared R BroschIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
David G ClarkIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Sophia WangIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
Rachael DeardorffIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Yu-Chien WuIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Sujuan GaoIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
Olaf SpornsIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Network Science Institute, Bloomington, IN, USA; Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Andrew J SaykinIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Network Science Institute, Bloomington, IN, USA. Electronic address: asaykin@iupui.edu.
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Indiana University School of MedicineIndiana University Bloomington · USIndiana University Health · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MPeripheral and Central Biomarkers of Alzheimer's Disease in Diverse CohortsU19AG074879 · NIA · MAYO CLINIC JACKSONVILLE · PI Minerva Maria Carrasquillo · 2023 to 2026
$42.0MResearch Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3MResearch Education ComponentP30AG072976 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI ANDREW J SAYKIN · 2021 to 2026
$24.1MUltrascale Machine Learning to Empower Discovery in Alzheimers Disease BiobanksU01AG068057 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christos Davatzikos, Heng Huang · 2020 to 2026
$20.7MKBASE2: Korean Brain Aging Study, Longitudinal Endophenotypes and Systems BiologyU01AG072177 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI LEE, DONG YOUNG, NHO, KWANGSIK TIMOTHY · 2021 to 2025
$11.2MOLDER BREAST CANCER PATIENTS: RISK FOR COGNITIVE DECLINER01CA129769 · NCI · GEORGETOWN UNIVERSITY · PI AHLES, TIM ALAN, MANDELBLATT, JEANNE · 2009 to 2020
$7.3MMemory Circuitry in MCI and Early Alzheimer’s Disease Prodrome: Molecular DriversR01AG019771 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 2001 to 2021
$6.9MSafety and modulation of ABCC9 pathways by nicorandil for the treatment of hippocampal sclerosis of aging (SMArTâHS)R01AG061111 · NIA · UNIVERSITY OF KENTUCKY · PI JICHA, GREGORY A, NELSON, PETER T. · 2019 to 2025
$3.6MLeveraging Neuroimaging Biomarkers to Understand the Role of Social Networks in Alzheimer's DiseaseR01AG057739 · NIA · TRUSTEES OF INDIANA UNIVERSITY · PI APOSTOLOVA, LIANA G, PERRY, BREA LOUISE · 2018 to 2022
$3.5MCognitive Aging, Alzheimers disease, and Cancer-related Cognitive DeclineR01AG068193 · NIA · GEORGETOWN UNIVERSITY · PI MANDELBLATT, JEANNE, SAYKIN, ANDREW J · 2020 to 2023
$2.8MNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA129769NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG072976NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG057739NIA NIH HHS R01 AG061111NIA NIH HHS R01 AG068193NIA NIH HHS R37 AG057739NIA NIH HHS U01 AG057195NIA NIH HHS U01 AG068057NIA NIH HHS U01 AG072177NIA NIH HHS U19 AG074879NLM NIH HHS R01 LM012535
Abstract
Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts. We identify AD susceptibility genes and gene modules in a gene co-expression network with expression profiles specifically related to regional vulnerability to Aβ and tau pathologies in AD. In addition, we identify distinct biochemical pathways associated with the gene-to-Aβ and the gene-to-tau associations. These findings may explain the discordance between regional Aβ and tau pathologies. Finally, we propose an analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations.
Indexed as
Alzheimer DiseaseCognitive DysfunctionAmyloid beta-PeptidesGene Expression ProfilingHumansTranscriptomeAmyloid beta-PeptidesAlzheimer’s diseaseamyloid-βbiochemical pathwayscognitive dysfunctionCP: Neurosciencegene expressiongene modulespathologyregional vulnerabilityspatial associationstau
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