Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease

BackgroundIron is an important component in neurofibrillary tangles, is known to co-localize with tangles in Alzheimer’s disease (AD) and can be measured using quantitative susceptibility mapping (QSM). However, it is unclear if iron measured using QSM is regionally related to tau in atypical presen...

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Main Authors: Neha Singh-Reilly, Ryota Satoh, Jonathan Graff-Radford, Mary M. Machulda, Val J. Lowe, Keith A. Josephs, Jennifer L. Whitwell
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Aging Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2025.1615718/full
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author Neha Singh-Reilly
Ryota Satoh
Jonathan Graff-Radford
Mary M. Machulda
Val J. Lowe
Keith A. Josephs
Jennifer L. Whitwell
author_facet Neha Singh-Reilly
Ryota Satoh
Jonathan Graff-Radford
Mary M. Machulda
Val J. Lowe
Keith A. Josephs
Jennifer L. Whitwell
author_sort Neha Singh-Reilly
collection DOAJ
description BackgroundIron is an important component in neurofibrillary tangles, is known to co-localize with tangles in Alzheimer’s disease (AD) and can be measured using quantitative susceptibility mapping (QSM). However, it is unclear if iron measured using QSM is regionally related to tau in atypical presentations of AD.MethodsForty patients with atypical AD underwent a 3 T magnetic resonance imaging (MRI) scan with a five-echo gradient echo sequence to calculate QSM, Aβ, and [18F] AV-1451 positron emission tomography (PET). The relationship between QSM and tau-PET was assessed using voxel-based regression analysis using whole brain VoxelStats and region-of-interest (ROI)-based Spearman’s correlation analyses using cortical and subcortical ROIs.ResultsAt the voxel-level, positive correlations between tau-PET and QSM were only observed in the left caudate. At the ROI-level, a positive association was observed between tau-PET and susceptibility in the occipital lobe and a negative association was observed between substantia nigra susceptibility and occipital tau-PET uptake, although these findings did not survive correction for multiple comparisons.DiscussionOur data provides little evidence that regional tau-PET uptake is related to susceptibility changes, suggesting that iron deposition may not be directly associated with tau accumulation in atypical AD.
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spelling doaj-art-32ddb9cc202f4ccd8b8d20c32d219d6b2025-08-20T03:31:10ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-07-011710.3389/fnagi.2025.16157181615718Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s diseaseNeha Singh-Reilly0Ryota Satoh1Jonathan Graff-Radford2Mary M. Machulda3Val J. Lowe4Keith A. Josephs5Jennifer L. Whitwell6Department of Radiology, Mayo Clinic, Rochester, MN, United StatesDepartment of Radiology, Mayo Clinic, Rochester, MN, United StatesDepartment of Neurology, Mayo Clinic, Rochester, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United StatesDepartment of Radiology, Mayo Clinic, Rochester, MN, United StatesDepartment of Neurology, Mayo Clinic, Rochester, MN, United StatesDepartment of Radiology, Mayo Clinic, Rochester, MN, United StatesBackgroundIron is an important component in neurofibrillary tangles, is known to co-localize with tangles in Alzheimer’s disease (AD) and can be measured using quantitative susceptibility mapping (QSM). However, it is unclear if iron measured using QSM is regionally related to tau in atypical presentations of AD.MethodsForty patients with atypical AD underwent a 3 T magnetic resonance imaging (MRI) scan with a five-echo gradient echo sequence to calculate QSM, Aβ, and [18F] AV-1451 positron emission tomography (PET). The relationship between QSM and tau-PET was assessed using voxel-based regression analysis using whole brain VoxelStats and region-of-interest (ROI)-based Spearman’s correlation analyses using cortical and subcortical ROIs.ResultsAt the voxel-level, positive correlations between tau-PET and QSM were only observed in the left caudate. At the ROI-level, a positive association was observed between tau-PET and susceptibility in the occipital lobe and a negative association was observed between substantia nigra susceptibility and occipital tau-PET uptake, although these findings did not survive correction for multiple comparisons.DiscussionOur data provides little evidence that regional tau-PET uptake is related to susceptibility changes, suggesting that iron deposition may not be directly associated with tau accumulation in atypical AD.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1615718/fullatypical Alzheimer’s diseaseQSMiron burdentau-PETtau accumulation
spellingShingle Neha Singh-Reilly
Ryota Satoh
Jonathan Graff-Radford
Mary M. Machulda
Val J. Lowe
Keith A. Josephs
Jennifer L. Whitwell
Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease
Frontiers in Aging Neuroscience
atypical Alzheimer’s disease
QSM
iron burden
tau-PET
tau accumulation
title Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease
title_full Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease
title_fullStr Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease
title_full_unstemmed Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease
title_short Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer’s disease
title_sort relationship between tau pet and quantitative susceptibility mapping in atypical alzheimer s disease
topic atypical Alzheimer’s disease
QSM
iron burden
tau-PET
tau accumulation
url https://www.frontiersin.org/articles/10.3389/fnagi.2025.1615718/full
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