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Clinicoanatomic localization of iron-rich gliosis in aphasic presentations of globular glial tauopathy.

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  1. [1] § Results ↔ process_ggt_data.ipynb, lines 212–339 · score 0.63 · cortical depth, iron stained, Pearson, correlation, intensity, DAB

Paper

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Overview

Authors: David J Irwin1, Sheina Emrani1, Daniel T Ohm1, Winifred Trotman1, Alejandra Bahena1, Eric Teunissen-Bermeo1, Philip Sabatini1, Sandhitsu R Das1, Gabor Mizsei2, Karthik Prabhakaran1, Ranjit Ittyerah1, H Branch Coslett1, Lauren Massimo1, David A Wolk1, John A Detre1,2, James C Gee2, Edward B Lee3, Paul Yushkevich2, Corey T McMillan1, M Dylan Tisdall2
ORCID iDs: David J Irwin, Daniel T Ohm, Edward B Lee, Paul Yushkevich, M Dylan Tisdall
  1. Department Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  2. Department Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  3. Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Institutions: University of Pennsylvania (United States)
Journal: Brain communications, volume 8, issue 3, article fcag169
Dates: received 14 November 2025; accepted 27 May 2026; published online 2 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1093/braincomms/fcag169 · PMID 42238478 · PMCID PMC13227947 · OpenAlex W7163220754
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: structural MRI / diffusion (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Connectivity
Keywords: globular glial tauopathy, iron, neuroinflammation, MRI, primary progressive aphasia
Topic: Epilepsy research and treatment (Psychiatry and Mental health, Medicine), according to OpenAlex
Funding: NIA NIH HHS (R01 AG056014, R01 AG069474, P30 AG072979)
Citations: not cited yet (Europe PMC); 30 references in the paper
Research resources: RRID:SCR_022398

Abstract

Globular glial tauopathy is a 4-repeat tauopathy associated with heterogenous clinical syndromes, including primary progressive aphasia. Iron-reactive gliosis in mid-to-deep cortical layers has previously been reported in this disorder, but detailed anatomic localization and its relationship to clinical symptoms is understudied, particularly within the anatomic framework of primary progressive aphasia. In a series of five autopsy-confirmed patients with globular glial tauopathy and one healthy control, we utilize ultra-high-resolution whole-hemisphere ex vivo 7 Telsa MRI and digital pathology to study whole-hemisphere and local laminar/cellular patterns of pathology within affected cortex. We find signature laminar patterns of iron-rich gliosis localized to brain regions implicated in distinct clinical aphasia syndromes between patients: patients who presented with non-fluent aphasia had iron-rich gliosis pathology localized to inferior and superior frontal and motor regions while iron-rich pathology was largely localized to the anterior temporal lobe in a patient with the semantic variant. Moreover, in one patient with non-fluent aphasia and additional iron-sensitive 7 Telsa MRI during life, we find evidence of antemortem iron-rich pathology in the same frontal regions observed post-mortem. These data suggest that focal neuroinflammation and iron dysregulation may contribute to the clinical expression of tauopathies and be detectable during life to improve diagnosis.

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

Repository

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picsl-ftdc-computational-pathology/ftdc_ggt_paper

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State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 7d82f7436f6d773d65d0367e580bfc795d54efa2, 13 January 2026
Languages: Jupyter (1)
Size: 153 files, 1 script
Software Heritage: not archived
Found in: “Data availability”
Holds: README, 1 notebook
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Matplotlib (1 file), NiBabel (1 file), NumPy (1 file), OpenCV (1 file), pandas (1 file), SciPy (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
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At the source: github.com/PICSL-FTDC-Computational-Pathology/FTDC_GGT_paper/tree/main

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

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Data

Datasets cited

Data availability

All MRI imaging data that support this study are openly available via Dryad at the following link: https://doi.org/10.5061/dryad.dbrv15fgk. All histopathology data that supports this study and tissue are available upon reasonable request from the authors, conditional on establishing a formal data sharing agreement with the University of Pennsylvania. Code for figure generation and laminar analysis and corresponding images are available at GithHub at the following link: https://github.com/PICSL-FTDC-Computational-Pathology/FTDC_GGT_paper/tree/main.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 20 authors, 5 keywords, 1 funder, 29 references, 1 RRID.

Cite

This paper

Irwin, D. J., Emrani, S., Ohm, D. T., Trotman, W., Bahena, A., Teunissen-Bermeo, E., Sabatini, P., Das, S. R., Mizsei, G., Prabhakaran, K., Ittyerah, R., Coslett, H. B., Massimo, L., Wolk, D. A., Detre, J. A., Gee, J. C., Lee, E. B., Yushkevich, P., McMillan, C. T., & Tisdall, M. D. (2026). Clinicoanatomic localization of iron-rich gliosis in aphasic presentations of globular glial tauopathy. Brain communications, 8(3), fcag169. https://doi.org/10.1093/braincomms/fcag169

BibTeX

@article{irwin2026clinicoanatomic,
author = {Irwin, David J and Emrani, Sheina and Ohm, Daniel T and Trotman, Winifred and Bahena, Alejandra and Teunissen-Bermeo, Eric and Sabatini, Philip and Das, Sandhitsu R and Mizsei, Gabor and Prabhakaran, Karthik and Ittyerah, Ranjit and Coslett, H Branch and Massimo, Lauren and Wolk, David A and Detre, John A and Gee, James C and Lee, Edward B and Yushkevich, Paul and McMillan, Corey T and Tisdall, M Dylan},
title = {{Clinicoanatomic localization of iron-rich gliosis in aphasic presentations of globular glial tauopathy}},
journal = {Brain communications},
year = {2026},
month = jun,
volume = {8},
number = {3},
pages = {fcag169},
publisher = {Oxford University Press},
issn = {2632-1297},
doi = {10.1093/braincomms/fcag169},
url = {https://doi.org/10.1093/braincomms/fcag169},
pmid = {42238478},
pmcid = {PMC13227947}
}

RIS

TY - JOUR
AU - Irwin, David J
AU - Emrani, Sheina
AU - Ohm, Daniel T
AU - Trotman, Winifred
AU - Bahena, Alejandra
AU - Teunissen-Bermeo, Eric
AU - Sabatini, Philip
AU - Das, Sandhitsu R
AU - Mizsei, Gabor
AU - Prabhakaran, Karthik
AU - Ittyerah, Ranjit
AU - Coslett, H Branch
AU - Massimo, Lauren
AU - Wolk, David A
AU - Detre, John A
AU - Gee, James C
AU - Lee, Edward B
AU - Yushkevich, Paul
AU - McMillan, Corey T
AU - Tisdall, M Dylan
TI - Clinicoanatomic localization of iron-rich gliosis in aphasic presentations of globular glial tauopathy
T2 - Brain communications
J2 - Brain Commun
PY - 2026
DA - 2026/06/02
VL - 8
IS - 3
SP - fcag169
SN - 2632-1297
PB - Oxford University Press
DO - 10.1093/braincomms/fcag169
UR - https://doi.org/10.1093/braincomms/fcag169
LA - en
ER -

CSL-JSON

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