---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21234'
abstract:
- lang: eng
  text: In aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan
    bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to
    cognitive decline in neurological diseases, they remain largely unstudied in the
    context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes
    in the aged hippocampus, with substantial variation among 32 inbred BXD mouse
    strains. Genetic mapping through quantitative trait locus analysis identified
    a major locus (Pgb1) that modulates hippocampal PGB burden. Extensive transcriptomic
    and proteomic datasets were produced for the aged hippocampus of the BXD family
    to investigate the mechanism by which the Pgb1 locus modulates PGB burden. We
    identified that Pgb1 contains allelic Smarcal1 and Usp37 variants and influences
    PGB burden through trans-regulation of mRNA and protein expression levels, including
    abundance of glycogen-mobilizing factor PYGB. Furthermore, comprehensive phenome-wide
    association scans, transcriptomic analyses, and direct behavioral testing demonstrated
    that cognition remains intact despite age-related PGB burden. A record of this
    paper’s transparent peer review process is included in the supplemental information.
acknowledgement: We would like to thank the Summer School Systems Genetics of Neural
  Ageing for bringing us together and spurring our international collaboration. We
  would also like to acknowledge the funding for the Summer School 2022 from the e:Med
  Systems Medicine Program of the BMBF (Bundesministerium für Bildung und Forschung;
  German Ministry of Education and Research) to R.W.O. In addition, we would like
  to thank the FLI imaging core facility for their assistance. A.G.-P. is supported
  by Fundación Séneca, Región de Murcia, Spain (21259/FPI/19). D.E.M.d.B. is financed
  by a Rubicon scholarship (452021116) from the Dutch Research Council (NWO). This
  work was also supported by NIH NIA R01AG070913-01 (R.W.W.), R01AG075813-01 (D.G.A.),
  and R01AG075818 (C.K.). We acknowledge the help of Larry Mobraaten (Jackson Laboratory,
  Bar Harbor, MN) with the BXD strains and U. Obermüller for the help with the histology.
  For the purpose of open access, the authors have applied a CC BY public copyright
  license to all author-accepted manuscripts arising from this submission.
article_number: '101488'
article_processing_charge: No
article_type: original
author:
- first_name: Alicia
  full_name: Gómez-Pascual, Alicia
  last_name: Gómez-Pascual
- first_name: Dow M
  full_name: Glikman, Dow M
  id: ab8acda1-91c1-11f0-aad8-f75d3d6424d8
  last_name: Glikman
- first_name: Hui Xin
  full_name: Ng, Hui Xin
  last_name: Ng
- first_name: James E.
  full_name: Tomkins, James E.
  last_name: Tomkins
- first_name: Lu
  full_name: Lu, Lu
  last_name: Lu
- first_name: Ying
  full_name: Xu, Ying
  last_name: Xu
- first_name: David G.
  full_name: Ashbrook, David G.
  last_name: Ashbrook
- first_name: Catherine
  full_name: Kaczorowski, Catherine
  last_name: Kaczorowski
- first_name: Gerd
  full_name: Kempermann, Gerd
  last_name: Kempermann
- first_name: John
  full_name: Killmar, John
  last_name: Killmar
- first_name: Khyobeni
  full_name: Mozhui, Khyobeni
  last_name: Mozhui
- first_name: Oliver
  full_name: Ohlenschläger, Oliver
  last_name: Ohlenschläger
- first_name: Rudolf
  full_name: Aebersold, Rudolf
  last_name: Aebersold
- first_name: Donald K.
  full_name: Ingram, Donald K.
  last_name: Ingram
- first_name: Evan G.
  full_name: Williams, Evan G.
  last_name: Williams
- first_name: Mathias
  full_name: Jucker, Mathias
  last_name: Jucker
- first_name: Rupert W.
  full_name: Overall, Rupert W.
  last_name: Overall
- first_name: Robert W.
  full_name: Williams, Robert W.
  last_name: Williams
- first_name: Dennis E.M.
  full_name: de Bakker, Dennis E.M.
  last_name: de Bakker
citation:
  ama: Gómez-Pascual A, Glikman DM, Ng HX, et al. The Smarcal1-Usp37 locus modulates
    glycogen aggregation in astrocytes of the aged hippocampus. <i>Cell Systems</i>.
    2026;17(2). doi:<a href="https://doi.org/10.1016/j.cels.2025.101488">10.1016/j.cels.2025.101488</a>
  apa: Gómez-Pascual, A., Glikman, D. M., Ng, H. X., Tomkins, J. E., Lu, L., Xu, Y.,
    … de Bakker, D. E. M. (2026). The Smarcal1-Usp37 locus modulates glycogen aggregation
    in astrocytes of the aged hippocampus. <i>Cell Systems</i>. Elsevier. <a href="https://doi.org/10.1016/j.cels.2025.101488">https://doi.org/10.1016/j.cels.2025.101488</a>
  chicago: Gómez-Pascual, Alicia, Dow M Glikman, Hui Xin Ng, James E. Tomkins, Lu
    Lu, Ying Xu, David G. Ashbrook, et al. “The Smarcal1-Usp37 Locus Modulates Glycogen
    Aggregation in Astrocytes of the Aged Hippocampus.” <i>Cell Systems</i>. Elsevier,
    2026. <a href="https://doi.org/10.1016/j.cels.2025.101488">https://doi.org/10.1016/j.cels.2025.101488</a>.
  ieee: A. Gómez-Pascual <i>et al.</i>, “The Smarcal1-Usp37 locus modulates glycogen
    aggregation in astrocytes of the aged hippocampus,” <i>Cell Systems</i>, vol.
    17, no. 2. Elsevier, 2026.
  ista: Gómez-Pascual A, Glikman DM, Ng HX, Tomkins JE, Lu L, Xu Y, Ashbrook DG, Kaczorowski
    C, Kempermann G, Killmar J, Mozhui K, Ohlenschläger O, Aebersold R, Ingram DK,
    Williams EG, Jucker M, Overall RW, Williams RW, de Bakker DEM. 2026. The Smarcal1-Usp37
    locus modulates glycogen aggregation in astrocytes of the aged hippocampus. Cell
    Systems. 17(2), 101488.
  mla: Gómez-Pascual, Alicia, et al. “The Smarcal1-Usp37 Locus Modulates Glycogen
    Aggregation in Astrocytes of the Aged Hippocampus.” <i>Cell Systems</i>, vol.
    17, no. 2, 101488, Elsevier, 2026, doi:<a href="https://doi.org/10.1016/j.cels.2025.101488">10.1016/j.cels.2025.101488</a>.
  short: A. Gómez-Pascual, D.M. Glikman, H.X. Ng, J.E. Tomkins, L. Lu, Y. Xu, D.G.
    Ashbrook, C. Kaczorowski, G. Kempermann, J. Killmar, K. Mozhui, O. Ohlenschläger,
    R. Aebersold, D.K. Ingram, E.G. Williams, M. Jucker, R.W. Overall, R.W. Williams,
    D.E.M. de Bakker, Cell Systems 17 (2026).
date_created: 2026-02-16T10:45:10Z
date_published: 2026-02-18T00:00:00Z
date_updated: 2026-02-23T10:35:01Z
day: '18'
ddc:
- '570'
department:
- _id: GradSch
doi: 10.1016/j.cels.2025.101488
external_id:
  pmid:
  - '41633365'
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file_date_updated: 2026-02-23T10:32:12Z
has_accepted_license: '1'
intvolume: '        17'
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language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Cell Systems
publication_identifier:
  issn:
  - 2405-4712
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the
  aged hippocampus
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2026'
...