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

**Authors:** Neha Singh-Reilly, Ryota Satoh, Jonathan Graff-Radford, Mary M. Machulda, Val J. Lowe, Keith A. Josephs, Jennifer L. Whitwell

PMC · DOI: 10.3389/fnagi.2025.1615718 · Frontiers in Aging Neuroscience · 2025-07-03

## TL;DR

This study investigates the relationship between tau and iron in atypical Alzheimer’s disease using brain imaging techniques, finding limited evidence of a direct link.

## Contribution

The study explores the regional relationship between tau-PET and QSM in atypical Alzheimer’s disease, which has not been well characterized.

## Key findings

- Positive correlations between tau-PET and QSM were only observed in the left caudate at the voxel-level.
- ROI analysis showed a positive association in the occipital lobe and a negative one in the substantia nigra, though not statistically significant after correction.
- Results suggest iron deposition may not directly correlate with tau accumulation in atypical Alzheimer’s disease.

## Abstract

Iron 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.

Forty 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.

At 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.

Our 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.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** AD (MESH:D000544), neurofibrillary tangles (MESH:D055956)
- **Chemicals:** [18F] AV-1451 (MESH:C000591008), Iron (MESH:D007501)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12267165/full.md

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Source: https://tomesphere.com/paper/PMC12267165