IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38376-x.html
   My bibliography  Save this article

Brain proteomic analysis implicates actin filament processes and injury response in resilience to Alzheimer’s disease

Author

Listed:
  • Zhi Huang

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Gennifer E. Merrihew

    (University of Washington)

  • Eric B. Larson

    (University of Washington)

  • Jea Park

    (University of Washington)

  • Deanna Plubell

    (University of Washington)

  • Edward J. Fox

    (Stanford University School of Medicine)

  • Kathleen S. Montine

    (Stanford University School of Medicine)

  • Caitlin S. Latimer

    (University of Washington)

  • C. Dirk Keene

    (University of Washington)

  • James Y. Zou

    (Stanford University School of Medicine)

  • Michael J. MacCoss

    (University of Washington)

  • Thomas J. Montine

    (Stanford University School of Medicine)

Abstract

Resilience to Alzheimer’s disease is an uncommon combination of high disease burden without dementia that offers valuable insights into limiting clinical impact. Here we assessed 43 research participants meeting stringent criteria, 11 healthy controls, 12 resilience to Alzheimer’s disease and 20 Alzheimer’s disease with dementia and analyzed matched isocortical regions, hippocampus, and caudate nucleus by mass spectrometry-based proteomics. Of 7115 differentially expressed soluble proteins, lower isocortical and hippocampal soluble Aβ levels is a significant feature of resilience when compared to healthy control and Alzheimer’s disease dementia groups. Protein co-expression analysis reveals 181 densely-interacting proteins significantly associated with resilience that were enriched for actin filament-based processes, cellular detoxification, and wound healing in isocortex and hippocampus, further supported by four validation cohorts. Our results suggest that lowering soluble Aβ concentration may suppress severe cognitive impairment along the Alzheimer’s disease continuum. The molecular basis of resilience likely holds important therapeutic insights.

Suggested Citation

  • Zhi Huang & Gennifer E. Merrihew & Eric B. Larson & Jea Park & Deanna Plubell & Edward J. Fox & Kathleen S. Montine & Caitlin S. Latimer & C. Dirk Keene & James Y. Zou & Michael J. MacCoss & Thomas J., 2023. "Brain proteomic analysis implicates actin filament processes and injury response in resilience to Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38376-x
    DOI: 10.1038/s41467-023-38376-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38376-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38376-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Brian C. Searle & Lindsay K. Pino & Jarrett D. Egertson & Ying S. Ting & Robert T. Lawrence & Brendan X. MacLean & Judit Villén & Michael J. MacCoss, 2018. "Chromatogram libraries improve peptide detection and quantification by data independent acquisition mass spectrometry," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Nicholas F. Fitz & Kyong Nyon Nam & Cody M. Wolfe & Florent Letronne & Brittany E. Playso & Bistra E. Iordanova & Takashi D. Y. Kozai & Richard J. Biedrzycki & Valerian E. Kagan & Yulia Y. Tyurina & X, 2021. "Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Fengchao Yu & Guo Ci Teo & Andy T. Kong & Klemens Fröhlich & Ginny Xiaohe Li & Vadim Demichev & Alexey I. Nesvizhskii, 2023. "Analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Masaji Sakaguchi & Shota Okagawa & Yuma Okubo & Yuri Otsuka & Kazuki Fukuda & Motoyuki Igata & Tatsuya Kondo & Yoshifumi Sato & Tatsuya Yoshizawa & Takaichi Fukuda & Kazuya Yamagata & Weikang Cai & Yu, 2022. "Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Ray Sajulga & Caleb Easterly & Michael Riffle & Bart Mesuere & Thilo Muth & Subina Mehta & Praveen Kumar & James Johnson & Bjoern Andreas Gruening & Henning Schiebenhoefer & Carolin A Kolmeder & Steph, 2020. "Survey of metaproteomics software tools for functional microbiome analysis," PLOS ONE, Public Library of Science, vol. 15(11), pages 1-20, November.
    4. Digant Nayak & Dongwen Lv & Yaxia Yuan & Peiyi Zhang & Wanyi Hu & Anindita Nayak & Eliza A. Ruben & Zongyang Lv & Patrick Sung & Robert Hromas & Guangrong Zheng & Daohong Zhou & Shaun K. Olsen, 2024. "Development and crystal structures of a potent second-generation dual degrader of BCL-2 and BCL-xL," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Juan F. Quintana & Praveena Chandrasegaran & Matthew C. Sinton & Emma M. Briggs & Thomas D. Otto & Rhiannon Heslop & Calum Bentley-Abbot & Colin Loney & Luis de Lecea & Neil A. Mabbott & Annette MacLe, 2022. "Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Marziah Hashimi & T. Andrew Sebrell & Jodi F. Hedges & Deann Snyder & Katrina N. Lyon & Stephanie D. Byrum & Samuel G. Mackintosh & Dan Crowley & Michelle D. Cherne & David Skwarchuk & Amanda Robison , 2023. "Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Rafaela Muniz de Queiroz & Gizem Efe & Asja Guzman & Naoko Hashimoto & Yusuke Kawashima & Tomoaki Tanaka & Anil K. Rustgi & Carol Prives, 2024. "Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    8. Klemens Fröhlich & Eva Brombacher & Matthias Fahrner & Daniel Vogele & Lucas Kook & Niko Pinter & Peter Bronsert & Sylvia Timme-Bronsert & Alexander Schmidt & Katja Bärenfaller & Clemens Kreutz & Oliv, 2022. "Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    9. Valdemaras Petrosius & Pedro Aragon-Fernandez & Nil Üresin & Gergo Kovacs & Teeradon Phlairaharn & Benjamin Furtwängler & Jeff Op De Beeck & Sarah L. Skovbakke & Steffen Goletz & Simon Francis Thomsen, 2023. "Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38376-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.