White Matter Hyperintensities Correlate with Accelerated Tau Accumulation in Posterior Cortical Regions in Alzheimer’s Disease

Sep 30, 2026

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Background: White matter hyperintensities (WMH) often co-exist with β-amyloid (Aβ) and tau tangles in Alzheimer’s disease (AD), yet links between WMH, Aβ plaques, and tau tangles remain unclear. Using two large datasets, the study evaluates how regional WMH relates to longitudinal tau accumulation. Method: 951 participants across ADNI and A4 cohorts used Aβ-PET, FLAIR MRI for WMH quantification via U-Net, and tau-PET, with RS-fMRI for subsets. It also quantifies connectivity-associated tau spread and compares cortical tau subtypes, then tests WMH impacts on tau accumulation within subtypes. Conclusion: Higher, especially occipital, WMH relates to faster tau accumulation and spread in posterior cortical regions independent of Aβ.

LanguageEnglish

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Abstract

Background

Method

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DOI: 10. 1002/alz70856_104870 BIOMARKERS PODIUM PRESENTATION NEUROIMAGING White Matter Hyperintensities Correlate with Accelerated Tau Accumulation in Posterior Cortical Regions in Alzheimer’s Disease Yue Cai 1 Jie Yang1, 2 Li Liang 1 Lili Fang 1 Xin Zhou 1, 3 Anqi Li 1, 4 Lin Liu 1 Pan Sun 1 Zhengbo He 1, 5 Yalin Zhu 1, 4 Yiying Wang 1 Mingxu Li 1, 6 Ting Ma7 Ying Han 1, 2, 3 Tengfei Guo 1, 8 1Shenzhen Bay Laboratory, Shenzhen, Guangdong, China 2Xuanwu Hospital of Capital Medical University, Beijing, Beijing, China 3 Hainan University, Haikou, Hainan, China 4The Hong Kong University of Science and Technology, Hongkong, Hongkong, China 5 Harbin Institute of Technology, Harbin, Heilongjiang, China 6The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China 7 Harbin Institute of Technology (Shenzhen), Shenzhen, Guangdong, China 8 Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China Correspondence Jie Yang, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China. [Email:](Email: yangjie@szbl.ac.cn)[ yangjie@szbl.ac.cn](Email: yangjie@szbl.ac.cn) Abstract Background: White matter hyperintensities (WMH) often co-exist with β-amyloid (Aβ) and tau tangles in Alzheimer’s disease (AD). However, the association of WMH, Aβ plaques, and tau tangles in AD remains elusive. Using two large datasets, this study comprehensively examined the relationship between regional WMH and longitudinal tau accumulation in AD. Method: A total of 951 participants from theADNI andA4 cohorts with Aβ-PET, fluidattenuated inversion recovery images (FLAIR), and tau-PET data were included, with Resting-state functional MRI (RS-fMRI) available for a subset of participants. FLAIR images were segmented using a U-Net deep learning model to obtain regional WMH volumes. Tau propagation along connectivity patterns was assessed using connectivityassociated tau spread metrics derived for the whole cortex and specific cortical regions (βGlobal , βFrontal , βParietal , βTemporal , and βOccipital ). We examined the associations between regional WMH, tau accumulation, and connectivity-associated tau spread. Additionally, two cortical tau subtypes were identified: “Occipital > Parietal” and“Parietal > Occipital”, characterized by higher or lower occipital tau relative to parietal tau, and the impact of regional WMH on tau accumulation was assessed within these subtypes. Result: Aβ+ individuals showed higher baseline levels and faster increases in total WMH compared to Aβ - individuals, but no differences were observed between T+ and T-individuals. Among Aβ+ individuals, temporal meta-ROI tau was not associated with faster WMH increases. However, greater total WMH was linked to accelerated temporal meta-ROI tau accumulation (Figure 1), although this relationship did not persist after controlling for Aβ. Greater occipital WMH was associated with faster tau This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e104870. [https://doi.org/10.1002/alz70856_104870](https://doi.org/10.1002/alz70856_104870) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of5 BIOMARKERS accumulation in occipital regions, particularly the cuneus, and with increasing βOccipital , independent of Aβ (Figure 2). The “Parietal > Occipital” subtype exhibited more rapid tau progression than the “Occipital > Parietal” subtype. In contrast, higher WMH was linked to faster tau increases in the cuneus exclusively within the latter subtype(Figure 3). Conclusion: Greater WMH burden, particularly in the occipital lobe, is associated with faster tau accumulation and spread in post

FAQs

What was the study’s main objective regarding WMH and tau in Alzheimer’s disease?

To determine how regional white matter hyperintensities relate to longitudinal tau accumulation in Alzheimer’s disease, and how this relationship interacts with Aβ status.

How were white matter hyperintensities measured in the study?

FLAIR images were segmented with a U-Net deep learning model to obtain regional WMH volumes.

What did the results show about the role of occipital WMH?

Greater occipital WMH was associated with faster tau accumulation in occipital regions, particularly the cuneus, and this relationship persisted independently of Aβ.

Sep 30, 2026

Uploaded by Marglet