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Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology

Author

Listed:
  • Prateek Kumar

    (Emory University School of Medicine
    Emory University School of Medicine
    Yale University School of Medicine)

  • Annie M. Goettemoeller

    (Emory University School of Medicine
    Emory University)

  • Claudia Espinosa-Garcia

    (Emory University School of Medicine
    Yale University School of Medicine)

  • Brendan R. Tobin

    (Georgia Institute of Technology)

  • Ali Tfaily

    (Yale University School of Medicine)

  • Ruth S. Nelson

    (Yale University School of Medicine)

  • Aditya Natu

    (Emory University School of Medicine)

  • Eric B. Dammer

    (Emory University School of Medicine
    Emory University)

  • Juliet V. Santiago

    (Emory University School of Medicine
    Emory University School of Medicine
    Emory University)

  • Sneha Malepati

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Lihong Cheng

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Hailian Xiao

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Duc D. Duong

    (Emory University School of Medicine
    Emory University)

  • Nicholas T. Seyfried

    (Emory University School of Medicine
    Emory University School of Medicine
    Emory University)

  • Levi B. Wood

    (Georgia Institute of Technology
    GeoInsrgia titute of Technology)

  • Matthew J. M. Rowan

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Srikant Rangaraju

    (Emory University School of Medicine
    Emory University School of Medicine
    Yale University School of Medicine)

Abstract

Dysfunction in fast-spiking parvalbumin interneurons (PV-INs) may represent an early pathophysiological perturbation in Alzheimer’s Disease (AD). Defining early proteomic alterations in PV-INs can provide key biological and translationally-relevant insights. We used cell-type-specific in-vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state PV-IN proteomes. PV-IN proteomic signatures include high metabolic and translational activity, with over-representation of AD-risk and cognitive resilience-related proteins. In bulk proteomes, PV-IN proteins were associated with cognitive decline in humans, and with progressive neuropathology in humans and the 5xFAD mouse model of Aβ pathology. PV-IN CIBOP in early stages of Aβ pathology revealed signatures of increased mitochondria and metabolism, synaptic and cytoskeletal disruption and decreased mTOR signaling, not apparent in whole-brain proteomes. Furthermore, we demonstrated pre-synaptic defects in PV-to-excitatory neurotransmission, validating our proteomic findings. Overall, in this study we present native-state proteomes of PV-INs, revealing molecular insights into their unique roles in cognitive resiliency and AD pathogenesis.

Suggested Citation

  • Prateek Kumar & Annie M. Goettemoeller & Claudia Espinosa-Garcia & Brendan R. Tobin & Ali Tfaily & Ruth S. Nelson & Aditya Natu & Eric B. Dammer & Juliet V. Santiago & Sneha Malepati & Lihong Cheng & , 2024. "Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47028-7
    DOI: 10.1038/s41467-024-47028-7
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    as
    1. Rebecca D. Hodge & Trygve E. Bakken & Jeremy A. Miller & Kimberly A. Smith & Eliza R. Barkan & Lucas T. Graybuck & Jennie L. Close & Brian Long & Nelson Johansen & Osnat Penn & Zizhen Yao & Jeroen Egg, 2019. "Conserved cell types with divergent features in human versus mouse cortex," Nature, Nature, vol. 573(7772), pages 61-68, September.
    2. Eugenio F. Fornasiero & Sunit Mandad & Hanna Wildhagen & Mihai Alevra & Burkhard Rammner & Sarva Keihani & Felipe Opazo & Inga Urban & Till Ischebeck & M. Sadman Sakib & Maryam K. Fard & Koray Kirli &, 2018. "Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    3. Najate Benamer & Marie Vidal & Maddalena Balia & María Cecilia Angulo, 2020. "Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    4. Hideji Murakoshi & Hong Wang & Ryohei Yasuda, 2011. "Local, persistent activation of Rho GTPases during plasticity of single dendritic spines," Nature, Nature, vol. 472(7341), pages 100-104, April.
    5. Bosiljka Tasic & Zizhen Yao & Lucas T. Graybuck & Kimberly A. Smith & Thuc Nghi Nguyen & Darren Bertagnolli & Jeff Goldy & Emma Garren & Michael N. Economo & Sarada Viswanathan & Osnat Penn & Trygve B, 2018. "Shared and distinct transcriptomic cell types across neocortical areas," Nature, Nature, vol. 563(7729), pages 72-78, November.
    6. Sruti Rayaprolu & Sara Bitarafan & Juliet V. Santiago & Ranjita Betarbet & Sydney Sunna & Lihong Cheng & Hailian Xiao & Ruth S. Nelson & Prateek Kumar & Pritha Bagchi & Duc M. Duong & Annie M. Goettem, 2022. "Cell type-specific biotin labeling in vivo resolves regional neuronal and astrocyte proteomic differences in mouse brain," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    8. Shinya Tasaki & Jishu Xu & Denis R. Avey & Lynnaun Johnson & Vladislav A. Petyuk & Robert J. Dawe & David A. Bennett & Yanling Wang & Chris Gaiteri, 2022. "Inferring protein expression changes from mRNA in Alzheimer’s dementia using deep neural networks," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Maria Antonietta Tosches & Heather J. Lee, 2023. "Cellular atlases of the entire mouse brain," Nature, Nature, vol. 624(7991), pages 253-255, December.
    10. David A. Barbie & Pablo Tamayo & Jesse S. Boehm & So Young Kim & Susan E. Moody & Ian F. Dunn & Anna C. Schinzel & Peter Sandy & Etienne Meylan & Claudia Scholl & Stefan Fröhling & Edmond M. Chan & Ma, 2009. "Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1," Nature, Nature, vol. 462(7269), pages 108-112, November.
    11. Tal Nuriel & Sergio L. Angulo & Usman Khan & Archana Ashok & Qiuying Chen & Helen Y. Figueroa & Sheina Emrani & Li Liu & Mathieu Herman & Geoffrey Barrett & Valerie Savage & Luna Buitrago & Efrain Cep, 2017. "Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer’s disease-like pathology," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
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