OSCR

Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains.

Overview

Authors: Jonathan AB Villareal1,2, Tim Bathe1,2,3,4,5, Ana de la Rosa1,2, Rohan V Sharma2, Elvin O Hernández Gómez2, Alison M Ryan6, Tara R Hawkinson6, Anthony M Tuzzolo1, Eduardo Medina-Parrilla1, Jennifer L Phillips1,2, Wangchen Tsering1,2,7,3, Andrea A Iturbe2,8, Benoit I Giasson2,8,3, Ramon C Sun2,3,9,6, Matthew S Gentry3,9,6, Stefan Prokop1,2,7,3
ORCID iDs: Jonathan AB Villareal, Tim Bathe, Wangchen Tsering
  1. Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
  2. Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA
  3. McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
  4. Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany
  5. Graduate School of Systemic Neurosciences (GSN), Department Biology II Neurobiology, LMU Munich, 82152 Planegg-Martinsried, Germany
  6. Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA
  7. Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL 32608, USA
  8. Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA
  9. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA
Institutions: University of Florida (United States); University of Florida Health (United States); Ludwig-Maximilians-Universität München (Germany)
Journal: Cell reports. Medicine, volume 7, issue 8, article 102968
Dates: received 18 August 2025; accepted 7 July 2026; published online 5 August 2026; in print August 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.xcrm.2026.102968 · PMID 42556344 · PMCID PMC13522764 · OpenAlex W7172550270
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: histology / microscopy (modality), human (organism), mouse (organism), Alzheimer's / dementia (population), clinical / translational (subfield)
Methods: fMRI & imaging
Keywords: Alzheimer’s disease, glycogen, tau, corpora amylacea, amyloid-β, metabolism
MeSH: Alzheimer Disease*, Brain*, Glycogen*, Aged, Aged, 80 and over, Animals, Female, Humans, Male, Mice, Neurofibrillary Tangles, Polysaccharides, tau Proteins (* major topic)
Topic: Glycogen Storage Diseases and Myoclonus (Rheumatology, Medicine), according to OpenAlex
Funding: NCI NIH HHS (R01 CA266004, R01 CA288696); National Institutes of Health; NIA NIH HHS (R01 AG078702, R01 AG066653, P30 AG066506); NINDS NIH HHS (RM1 NS133593); Evelyn F. and William L. McKnight Brain Institute, University of Florida Health; National Cancer Institute Division of Cancer Epidemiology and Genetics (R01CA266004, 1R01CA288696-01); National Institute of General Medical Sciences (T32GM163993); National Institute on Aging (P30AG066506, R01AG078702, R01AG066653); National Institute of Neurological Disorders and Stroke (RM1NS133593); NIGMS NIH HHS (T32 GM163993)
Citations: not cited yet (Europe PMC); 68 references in the paper
Research resources: Rabbit anti-Aβ RRID:AB_2797713, Rabbit anti-Iba1 RRID:AB_2832244, Rabbit anti-MAP2 RRID:AB_2889161, Rabbit anti-GFAP RRID:AB_60418

Abstract

Increasing evidence indicates that shifts in brain polysaccharide metabolism can influence the progression of multiple neurodegenerative diseases. Here, we profile corpora amylacea (CA) in 230 postmortem human brains, revealing significantly higher densities in Alzheimer’s disease (AD) patients when compared with patients with other or no neurodegenerative diseases and a tight correlation of CA density with neurofibrillary tangle (NFT) pathology. Immunohistochemical profiling using an anti-glycogen antibody confirms the polysaccharide nature of CA and reveals plaque-like glycogen patches (GPs) and densely aggregated intraneuronal glycogen in AD patient brains correlated with the emergence of NFT pathology. matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) orthogonally verifies the polysaccharide identity of these structures and that GPs can be consistently observed at early neuropathological disease stages. GPs are also observed in murine models of AD-like pathology, correlating with tau pathology. The identification of these AD-associated glycogen pathologies in the human brain implies that alterations in glycogen metabolism are tightly associated with AD pathogenesis.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

doi:10.7910/dvn/sougim

License: none: the authors keep all their rights
State: unreachable at the last attempt, verified on 29 September 2026
Evidence: found in the paper
Software Heritage: not checked
Found in: “Data and code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 5 checks, the latest on 29 September 2026: unreachable at the last attempt (HTTP 202)
  • 29 September 2026: unreachable at the last attempt (HTTP 202)
  • 28 September 2026: unreachable at the last attempt (HTTP 202)
  • 28 September 2026: unreachable at the last attempt (HTTP 202)
  • 27 September 2026: unreachable at the last attempt (HTTP 202)
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At the source: doi.org/10.7910/dvn/sougim

forum.image.sc/t/script-for-average-non-cell-detection-area-in-multiple-annotations

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: the link answers
Software Heritage: not checked
Found in: the text, “PAS-stained CA, IV58B6-stained glycogen, and IV5”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
  • 27 September 2026: the link answers (HTTP 200)
At the source: forum.image.sc/t/script-for-average-non-cell-detection-area-in-multiple-annotations/107595

The paper's code and data availability statement is in the Data section.

Tracing map

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  • no match between paragraphs and code yet;
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Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

Data and code availability

Datasets used for image and mass spectroscopy (MALDI) analysis are available and deposited in Harvard Dataverse: https://doi.org/10.7910/DVN/ISYQVC and in MetaboLights: MTBLS14754 (also listed in the STAR Methods key resources table).

QuPath scripts and additional code utilized in this study are available and deposited in Harvard Dataverse: https://doi.org/10.7910/DVN/SOUGIM (also listed in the STAR Methods key resources table).

Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 3, 28 September 2026

  • Authors: added Jonathan AB Villareal (0009-0008-9450-4520); removed Jonathan AB Villareal

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 6 keywords, 13 MeSH terms, 10 funders, 68 references, 4 RRIDs.

Cite

This paper

Villareal, J. A., Bathe, T., Rosa, A. d. l., Sharma, R. V., Hernández Gómez, E. O., Ryan, A. M., Hawkinson, T. R., Tuzzolo, A. M., Medina-Parrilla, E., Phillips, J. L., Tsering, W., Iturbe, A. A., Giasson, B. I., Sun, R. C., Gentry, M. S., & Prokop, S. (2026). Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains. Cell reports. Medicine, 7(8), 102968. https://doi.org/10.1016/j.xcrm.2026.102968

BibTeX

@article{villareal2026corpora,
author = {Villareal, Jonathan AB and Bathe, Tim and Rosa, Ana de la and Sharma, Rohan V and Hernández Gómez, Elvin O and Ryan, Alison M and Hawkinson, Tara R and Tuzzolo, Anthony M and Medina-Parrilla, Eduardo and Phillips, Jennifer L and Tsering, Wangchen and Iturbe, Andrea A and Giasson, Benoit I and Sun, Ramon C and Gentry, Matthew S and Prokop, Stefan},
title = {{Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains}},
journal = {Cell reports. Medicine},
year = {2026},
month = aug,
volume = {7},
number = {8},
pages = {102968},
publisher = {Elsevier},
issn = {2666-3791},
doi = {10.1016/j.xcrm.2026.102968},
url = {https://doi.org/10.1016/j.xcrm.2026.102968},
pmid = {42556344},
pmcid = {PMC13522764}
}

RIS

TY - JOUR
AU - Villareal, Jonathan AB
AU - Bathe, Tim
AU - Rosa, Ana de la
AU - Sharma, Rohan V
AU - Hernández Gómez, Elvin O
AU - Ryan, Alison M
AU - Hawkinson, Tara R
AU - Tuzzolo, Anthony M
AU - Medina-Parrilla, Eduardo
AU - Phillips, Jennifer L
AU - Tsering, Wangchen
AU - Iturbe, Andrea A
AU - Giasson, Benoit I
AU - Sun, Ramon C
AU - Gentry, Matthew S
AU - Prokop, Stefan
TI - Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains
T2 - Cell reports. Medicine
J2 - Cell Rep Med
PY - 2026
DA - 2026/08/05
VL - 7
IS - 8
SP - 102968
SN - 2666-3791
PB - Elsevier
DO - 10.1016/j.xcrm.2026.102968
UR - https://doi.org/10.1016/j.xcrm.2026.102968
LA - en
ER -

CSL-JSON

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