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White matter structure-function coupling alteration is associated with plasma biomarkers and cognition in Alzheimer's disease.

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Title: White matter structure-function coupling alteration is associated with plasma biomarkers and cognition in Alzheimer's disease.
Authors: Guo, Yihao1 (AUTHOR), Liu, Tao2 (AUTHOR) ltao829@163.com, Chen, Huijuan1 (AUTHOR), Huang, Weiyuan1 (AUTHOR), Zhang, Kun2 (AUTHOR), Chen, Feng1,3 (AUTHOR) fenger0802@hainmc.edu.cn
Source: European Radiology. Nov2025, Vol. 35 Issue 11, p7053-7063. 11p.
Subjects: Alzheimer's disease, White matter (Nerve tissue), Neuropsychological tests, Cognition, Biomarkers, Knowledge transfer, Functional connectivity
Abstract: Objectives: There were white matter (WM) microstructural abnormalities in Alzheimer's disease (AD), and it may affect information transmission along WM tracts. We aim to investigate AD-related changes in the structure-function coupling of WM and their associations with AD plasma biomarkers and cognitive performance. Methods: This retrospective study evaluated participants who provided blood samples, underwent MR brain scans, and completed neuropsychological assessments. Plasma biomarker levels of β-amyloid (Aβ), phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured using the Single Molecule Array platform. We used a structure-function coupling approach, combining spatial-temporal correlations of functional signals with diffusion tensor orientations in the WM circuit derived from functional and diffusion magnetic resonance imaging (MRI). Association and mediation analyses were conducted to explore the relationships among plasma biomarkers, structure-function coupling, and cognitive performance in AD. Results: Compared with the cognitively normal (CN) and mild cognitive impairment (MCI) groups, the AD dementia group showed a widespread increase in structure-function coupling within WM regions, including the body and splenium of the corpus callosum. Additionally, structure-function coupling in WM tracts was significantly associated with the levels of p-tau181 and NfL. Moreover, structure-function coupling mediated the relationship between memory and the level of p-tau181 or NfL. Conclusion: Our findings suggest that there is altered information transmission along WM tracts in patients with AD. The brain structure-function coupling is associated with plasma biomarkers and cognitive scores, suggesting that abnormal signal transfer of neuronal fiber pathways could be a potential mechanism of AD neuropathology. Key Points: QuestionWhite matter (WM) microstructural abnormalities may affect information transmission along WM tracts, resulting in cognitive decline in Alzheimer's disease (AD). FindingsThe AD dementia group showed a widespread increase in structure-function coupling within WM regions, which was associated with plasma biomarkers and cognitive scores. Clinical relevanceThe brain structure-function coupling is associated with plasma biomarkers and cognitive scores, suggesting that abnormal signal transfer of neuronal fiber pathways could be a potential mechanism of the neuropathology of AD. [ABSTRACT FROM AUTHOR]
Copyright of European Radiology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: White matter structure-function coupling alteration is associated with plasma biomarkers and cognition in Alzheimer's disease.
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  Data: <searchLink fieldCode="AR" term="%22Guo%2C+Yihao%22">Guo, Yihao</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Tao%22">Liu, Tao</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> ltao829@163.com</i><br /><searchLink fieldCode="AR" term="%22Chen%2C+Huijuan%22">Chen, Huijuan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Weiyuan%22">Huang, Weiyuan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Kun%22">Zhang, Kun</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Feng%22">Chen, Feng</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<i> fenger0802@hainmc.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22European+Radiology%22">European Radiology</searchLink>. Nov2025, Vol. 35 Issue 11, p7053-7063. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22White+matter+%28Nerve+tissue%29%22">White matter (Nerve tissue)</searchLink><br /><searchLink fieldCode="DE" term="%22Neuropsychological+tests%22">Neuropsychological tests</searchLink><br /><searchLink fieldCode="DE" term="%22Cognition%22">Cognition</searchLink><br /><searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Knowledge+transfer%22">Knowledge transfer</searchLink><br /><searchLink fieldCode="DE" term="%22Functional+connectivity%22">Functional connectivity</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objectives: There were white matter (WM) microstructural abnormalities in Alzheimer's disease (AD), and it may affect information transmission along WM tracts. We aim to investigate AD-related changes in the structure-function coupling of WM and their associations with AD plasma biomarkers and cognitive performance. Methods: This retrospective study evaluated participants who provided blood samples, underwent MR brain scans, and completed neuropsychological assessments. Plasma biomarker levels of β-amyloid (Aβ), phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured using the Single Molecule Array platform. We used a structure-function coupling approach, combining spatial-temporal correlations of functional signals with diffusion tensor orientations in the WM circuit derived from functional and diffusion magnetic resonance imaging (MRI). Association and mediation analyses were conducted to explore the relationships among plasma biomarkers, structure-function coupling, and cognitive performance in AD. Results: Compared with the cognitively normal (CN) and mild cognitive impairment (MCI) groups, the AD dementia group showed a widespread increase in structure-function coupling within WM regions, including the body and splenium of the corpus callosum. Additionally, structure-function coupling in WM tracts was significantly associated with the levels of p-tau181 and NfL. Moreover, structure-function coupling mediated the relationship between memory and the level of p-tau181 or NfL. Conclusion: Our findings suggest that there is altered information transmission along WM tracts in patients with AD. The brain structure-function coupling is associated with plasma biomarkers and cognitive scores, suggesting that abnormal signal transfer of neuronal fiber pathways could be a potential mechanism of AD neuropathology. Key Points: QuestionWhite matter (WM) microstructural abnormalities may affect information transmission along WM tracts, resulting in cognitive decline in Alzheimer's disease (AD). FindingsThe AD dementia group showed a widespread increase in structure-function coupling within WM regions, which was associated with plasma biomarkers and cognitive scores. Clinical relevanceThe brain structure-function coupling is associated with plasma biomarkers and cognitive scores, suggesting that abnormal signal transfer of neuronal fiber pathways could be a potential mechanism of the neuropathology of AD. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Group: Ab
  Data: <i>Copyright of European Radiology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – SubjectFull: Alzheimer's disease
        Type: general
      – SubjectFull: White matter (Nerve tissue)
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      – SubjectFull: Neuropsychological tests
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      – SubjectFull: Cognition
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      – SubjectFull: Knowledge transfer
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      – SubjectFull: Functional connectivity
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      – TitleFull: White matter structure-function coupling alteration is associated with plasma biomarkers and cognition in Alzheimer's disease.
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              Text: Nov2025
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