ArticleNeuron2025
Distinct systemic impacts of Aβ42 and Tau revealed by whole-organism snRNA-seq.
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Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
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Who cites it
16 citing papers in PubMed.
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- Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila.PLoS genetics · 2026Article
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- Intrinsic regulation of intestinal stem cell fate and homeostasis by Tet.bioRxiv : the preprint server for biology · 2026Article
- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An snRNA-seq aging clock for the fruit fly head sheds light on sex-biased aging.Scientific reports · 2026Article
- Amyloid beta 42 disrupts cardiac function in Alzheimer's disease mice via SLC31A1 upregulation-mediated cuproptosis.Basic research in cardiology · 2026Article
- A high-resolution atlas of the brain predicts lineage and birth order underlying neuronal identity.Cell genomics · 2026Article
- Differential neuronal survival defines a novel axis of sexual dimorphism in the Drosophila brain.Cell genomics · 2026Article
- Prognostic impact of baseline blood biomarkers in SCLC first-line treatment.Therapeutic advances in medical oncology · 2026Article
- Hippo signaling regulates cuticle pigmentation and dopamine metabolism inbioRxiv : the preprint server for biology · 2025Article
- Neuronal glycolytic reprogramming drives lethality via accelerated aging in abioRxiv : the preprint server for biology · 2025Article
- Article
- The transcriptional and cellular landscape of cognitive resilience to Alzheimer's disease.Frontiers in molecular neuroscience · 2025Review
- Toward precision longevity: aging interventions in the single-cell atlas era.Frontiers in aging · 2025Review
Corrections and comments
- Update of
Authors and funding
20 authors.
Ye-Jin ParkHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Program in Development, Disease Models & Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA.
Tzu-Chiao LuHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Tyler JacksonHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Cancer Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Lindsey D GoodmanDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
Lindsey RanHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jiaye ChenHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Chung-Yi LiangHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Erin HarrisonHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Christina KoHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Xi ChenUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Baiping WangHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Ao-Lin HsuInstitute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Department of Internal Medicine, Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor, MI 28109, USA.
Elizabeth OchoaGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA.
Kevin F BieniekGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA; Department of Pathology & Laboratory Medicine, UT Health San Antonio, San Antonio, TX 78229, USA.
Shinya YamamotoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Program in Development, Disease Models & Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Yi ZhuUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Hui ZhengHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Yanyan QiHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Hugo J BellenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Program in Development, Disease Models & Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hbellen@bcm.edu.
Hongjie LiHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hongjie.li@bcm.edu.
Funding
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Sudha Seshadri · 2021 to 2026
$24.0MTransposon induced disruption of most Drosophila genesR01GM067858 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2003 to 2020
$15.7MTMEM106b as a lysosomal adaptor to influence brain aging and tau pathogenesisP01AG066606 · NIA · BAYLOR COLLEGE OF MEDICINE · PI JANKOWSKY, JOANNA L · 2021 to 2025
$13.5MFunctional Genomic Dissection of Alzheimer's Disease in Humans and Drosophila ModelsU01AG072439 · NIA · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J, BOTAS, JUAN · 2021 to 2025
$8.4MSan Antonio Biomedical Education and ResearchK12GM111726 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LECHLEITER, JAMES D, OYAJOBI, BABATUNDE OLUKAYODE · 2015 to 2024
$7.6MA Comprehensive Resource for Manipulating the Drosophila GenomeR24OD031447 · OD · BAYLOR COLLEGE OF MEDICINE · PI HUGO J BELLEN, Oguz Kanca · 2021 to 2026
$5.2MMutidisciplinary Training;Brain Disorders &DevelopmentT32NS043124 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI SWANN, JOHN WILLIAM · 2002 to 2021
$4.6MROLE OF TFEB IN TAUOPATHYR01NS093652 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ZHENG, HUI · 2015 to 2025
$3.1MThe Clinical Translational Research Certificate of Added Qualification ProgramT32GM136554 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Melissa Suter, IGNATIA B VAN DEN VEYVER · 2020 to 2026
$3.0MIMPACTS OF GLIAL LIPID DROPLETS ON OXIDATIVE STRESS AND NEURODEGENERATION IN ALZHEIMER'S DISEASER01AG073260 · NIA · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2021 to 2025
$2.6MKnockin mouse models of Alzheimer's DiseaseRF1AG020670 · NIA · BAYLOR COLLEGE OF MEDICINE · PI ZHENG, HUI · 2022 to 2022
$2.3MInterorgan communication in aging in DrosophilaU01AG086143 · NIA · HARVARD MEDICAL SCHOOL · PI Hongjie Li, NORBERT PERRIMON · 2024 to 2026
$2.0MNIA NIH HHS P01 AG066606NIA NIH HHS P30 AG066546NIA NIH HHS R01 AG071557NIA NIH HHS R01 AG073260NIA NIH HHS RF1 AG020670NIA NIH HHS RF1 AG071557NIA NIH HHS U01 AG072439NIA NIH HHS U01 AG086143NIDDK NIH HHS R01 DK136532NIDDK NIH HHS R01 DK136619NIGMS NIH HHS K12 GM111726NIGMS NIH HHS R01 GM067858NIGMS NIH HHS T32 GM136554NIH HHS R24 OD031447NINDS NIH HHS R01 NS093652NINDS NIH HHS T32 NS043124
Abstract
Both neuronal and peripheral tissues become disrupted in Alzheimer's disease (AD). However, a comprehensive understanding of how AD impacts different tissues across the whole organism is lacking. Using Drosophila, we generated an AD Fly Cell Atlas (AD-FCA) based on whole-organism single-nucleus transcriptomes of 219 cell types from flies expressing AD-associated proteins, either human amyloid-β 42 peptide (Aβ42) or Tau, in neurons. We found that Aβ42 primarily affects the nervous system, including sensory neurons, while Tau induces accelerated aging in peripheral tissues. We identified a neuronal cluster enriched in Aβ42 flies, which has high lactate dehydrogenase (LDH) expression. This LDH-high cluster is conserved in 5XFAD mouse and human AD datasets. We found a conserved defect in fat metabolism from both fly and mouse tauopathy models. The AD-FCA offers new insights into how Aβ42 or Tau systemically and differentially affects a whole organism and provides a valuable resource for understanding brain-body communication in neurodegeneration.
Indexed as
Alzheimer DiseaseAmyloid beta-PeptidesPeptide Fragmentstau ProteinsAnimalsDisease Models, AnimalDrosophilaHumansMiceMice, TransgenicNeuronsTauopathiesTranscriptomeAmyloid beta-Peptidesamyloid beta-protein (1-42)Peptide Fragmentstau ProteinsagingAlzheimer’s diseasebrain-body communicationcell atlasDrosophilaLDH-high clusterneurodegenerationsingle-nucleus RNA-seq
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.