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Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

Author

Listed:
  • Angela M. Crist

    (Department of Neuroscience, Mayo Clinic)

  • Kelly M. Hinkle

    (Department of Neuroscience, Mayo Clinic)

  • Xue Wang

    (Department of Health Sciences Research, Mayo Clinic)

  • Christina M. Moloney

    (Department of Neuroscience, Mayo Clinic)

  • Billie J. Matchett

    (Department of Neuroscience, Mayo Clinic)

  • Sydney A. Labuzan

    (Department of Neuroscience, Mayo Clinic)

  • Isabelle Frankenhauser

    (Department of Neuroscience, Mayo Clinic
    Paracelsus Medical Private University)

  • Nkem O. Azu

    (Department of Neuroscience, Mayo Clinic)

  • Amanda M. Liesinger

    (Department of Neuroscience, Mayo Clinic)

  • Elizabeth R. Lesser

    (Department of Health Sciences Research, Mayo Clinic)

  • Daniel J. Serie

    (Department of Health Sciences Research, Mayo Clinic)

  • Zachary S. Quicksall

    (Department of Health Sciences Research, Mayo Clinic)

  • Tulsi A. Patel

    (Department of Neuroscience, Mayo Clinic)

  • Troy P. Carnwath

    (Department of Neuroscience, Mayo Clinic)

  • Michael DeTure

    (Department of Neuroscience, Mayo Clinic)

  • Xiaojia Tang

    (Department of Health Sciences Research, Mayo Clinic)

  • Ronald C. Petersen

    (Department of Neurology, Mayo Clinic)

  • Ranjan Duara

    (Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center)

  • Neill R. Graff-Radford

    (Department of Neurology, Mayo Clinic)

  • Mariet Allen

    (Department of Neuroscience, Mayo Clinic)

  • Minerva M. Carrasquillo

    (Department of Neuroscience, Mayo Clinic)

  • Hu Li

    (Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic)

  • Owen A. Ross

    (Department of Neuroscience, Mayo Clinic)

  • Nilüfer Ertekin-Taner

    (Department of Neuroscience, Mayo Clinic
    Department of Neurology, Mayo Clinic)

  • Dennis W. Dickson

    (Department of Neuroscience, Mayo Clinic)

  • Yan W. Asmann

    (Department of Health Sciences Research, Mayo Clinic)

  • Rickey E. Carter

    (Department of Health Sciences Research, Mayo Clinic)

  • Melissa E. Murray

    (Department of Neuroscience, Mayo Clinic)

Abstract

Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

Suggested Citation

  • Angela M. Crist & Kelly M. Hinkle & Xue Wang & Christina M. Moloney & Billie J. Matchett & Sydney A. Labuzan & Isabelle Frankenhauser & Nkem O. Azu & Amanda M. Liesinger & Elizabeth R. Lesser & Daniel, 2021. "Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22399-3
    DOI: 10.1038/s41467-021-22399-3
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    Cited by:

    1. Bidur Paudel & Si-Yeon Jeong & Carolina Pena Martinez & Alexis Rickman & Ashley Haluck-Kangas & Elizabeth T. Bartom & Kristina Fredriksen & Amira Affaneh & John A. Kessler & Joseph R. Mazzulli & Andre, 2024. "Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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