TY - JOUR
T1 - Quantitative susceptibility mapping of the brain is associated with inflammatory changes in Alzheimer’s disease related areas
AU - Hosseini, Seyyed Ali
AU - Servaes, Stijn
AU - Macedo, Arthur C.
AU - Aumont, Etienne
AU - Rahmouni, Nesrine
AU - Chan, Tevy
AU - Therriault, Joseph
AU - Trudel, Lydia
AU - Hall, Brandon
AU - Wang, Yi Ting
AU - Arias, Jaime Fernandez
AU - Bezgin, Gleb
AU - Zheng, Yansheng
AU - Gonçalves, Marina P.
AU - Quispialaya Socualaya, Kely
AU - Woo, Marcel S.
AU - Tissot, Cécile
AU - Oliva-Lopez, Delphine
AU - Li, Jieying
AU - Mitchell, Stuart
AU - Lebrun, Aurélie
AU - Hopewell, Robert
AU - Chawla, Sanjeev
AU - Fonov, Vladimir
AU - Massarweh, Gassan
AU - Medina, Yasser Iturria
AU - Soucy, Jean Paul
AU - Montembeault, Maxime
AU - Vitali, Paolo
AU - Blennow, Kaj
AU - Karikari, Thomas K.
AU - Benedet, Andréa L.
AU - Ashton, Nicholas J.
AU - Zetterberg, Henrik
AU - Pascoal, Tharick A.
AU - Gauthier, Serge
AU - Klostranec, Jesse
AU - Zhuang, Hangwei
AU - Cho, Junghun
AU - Collins, D. Louis
AU - Wang, Yi
AU - Rudko, David A.
AU - Rosa-Neto, Pedro
N1 - Publisher Copyright:
© The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
PY - 2026/7
Y1 - 2026/7
N2 - Accumulation of paramagnetic substances in brain tissue may constitute a feature of Alzheimer’s disease (AD) associated with inflammatory processes. This study employed MRI quantitative susceptibility mapping (QSM), as an index of paramagnetic load, to assess its association with brain Aβ and tau aggregates, as well as inflammatory biomarkers. We assessed QSM and T1-weighted MRI scans from 315 participants in the TRIAD cohort, including young-controls and individuals across the AD spectrum. Imaging was performed at baseline, with follow-up assessments at 12 and 24 months. Mean-cortical and subcortical susceptibility values were measured, and correlations with AD-relevant plasma and CSF inflammatory biomarkers. At baseline, AD patients had significantly greater QSM than age-matched controls in the posterior cingulate cortex, precuneus, and basal ganglia. After 24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers IL-10RB, PD-L1, SCF, TWEAK, CSF-1, CXCL9, HGF, and CD40, but not with brain Aβ or tau-related biomarkers. Our findings reveal that the magnitude of tissue susceptibility load, as measured by QSM, reflects tissue inflammation rather than protein aggregation. QSM provides new insights into tissue dysfunction, with potential applications in AD therapeutic development.
AB - Accumulation of paramagnetic substances in brain tissue may constitute a feature of Alzheimer’s disease (AD) associated with inflammatory processes. This study employed MRI quantitative susceptibility mapping (QSM), as an index of paramagnetic load, to assess its association with brain Aβ and tau aggregates, as well as inflammatory biomarkers. We assessed QSM and T1-weighted MRI scans from 315 participants in the TRIAD cohort, including young-controls and individuals across the AD spectrum. Imaging was performed at baseline, with follow-up assessments at 12 and 24 months. Mean-cortical and subcortical susceptibility values were measured, and correlations with AD-relevant plasma and CSF inflammatory biomarkers. At baseline, AD patients had significantly greater QSM than age-matched controls in the posterior cingulate cortex, precuneus, and basal ganglia. After 24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers IL-10RB, PD-L1, SCF, TWEAK, CSF-1, CXCL9, HGF, and CD40, but not with brain Aβ or tau-related biomarkers. Our findings reveal that the magnitude of tissue susceptibility load, as measured by QSM, reflects tissue inflammation rather than protein aggregation. QSM provides new insights into tissue dysfunction, with potential applications in AD therapeutic development.
KW - Alzheimer’s disease
KW - QSM
KW - brain’ susceptibility
KW - immune biomarkers
KW - neuroinflammation
UR - https://www.scopus.com/pages/publications/105029453746
U2 - 10.1177/0271678X261417193
DO - 10.1177/0271678X261417193
M3 - Article
AN - SCOPUS:105029453746
SN - 0271-678X
VL - 46
SP - 1841
EP - 1856
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 7
ER -