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Disrupted white matter functional connectivity in aMCI APOEε4 carriers: a resting-state study

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Abstract

The ε4 allele of the APOE gene is thought to increase risk from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. Cognitive decline in the condition is increasingly considered to worsen functional disconnections in brain network composed of gray matter and white matter. Nevertheless, Whether APOEε4 targets specific white matter functional connectivity in patients with aMCI remains mostly unexplored, mainly due to the challenges of detecting BOLD signals in white matter. Here, we applied a novel approach to investigate APOEε4-related specific bundles and cortical area alterations in aMCI subjects, in order to characterize white matter-gray matter functional connectivity differences throughout the brain. We analyzed 75 patients with aMCI and 76 demographically matched normal controls. The aMCI APOEε4 carriers showed decreased functional connectivity located at left corticospinal tract, bilateral posterior limb of internal capsule, and right temporopolaris, which was different from the regions of aMCI-related changes. We further found that recognition scores were positively associated with the right temporopolaris in aMCI APOEε4 carriers. Collectively, the data provide new evidence that APOEε4 genotype exerts a negative impact on neural activity in both gray and white matter in aMCI, which potentially contributes to functional disconnection and memory decline. A novel method provides full-scale measuring effect of disease conditions on functional architecture throughout the brain. Trial registration: https://www.ClinicalTrials.gov (Identifier: NCT02225964). Registered January 2014.

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Acknowledgements

We thank the dedicated participants and staff of Xuanwu Hospital for data collection, including Yu Sun, **aoni Wang, Guanqun Chen, Weina Zhao, Bin Mu, Ziqi Wang, Yuxia Li, Ying Chen, Xuanyu Li, Wenying Du, Jiachen Li, **ng Zhao, Qin Yang, **aoqi Wang, Jun Wang, and Liu Yang.

Funding

This work was supported by The National Key Research and Development Program of China (2016YFC1306300, 2018YFC1312001), National Natural Science Foundation of China (Grant 61633018, 81871438).

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Authors and Affiliations

  1. Department of Neurology, Xuanwu Hospital of Capital Medical University, Bei**g, China

    Hua Lin, Li Lin, Shimin Hu & Ying Han

  2. University Institute of Imaging Science, Vanderbilt University, Nashville, TN, 37232, USA

    Muwei Li

  3. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Muwei Li

  4. School of Mechanical, Electrical and Information Engineering, Shandong University, **an, China

    Yang Zhan

  5. Department of Evidence-Based Medicine, Xuanwu Hospital of Capital Medical University, Bei**g, China

    Kun Yang

  6. National Clinical Research Center for Geriatric Disorders, Bei**g, China

    Ying Han

  7. Center of Alzheimer’s Disease , Bei**g Institute for Brain Disorders , Bei**g, China

    Ying Han

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  1. Hua Lin
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Correspondence to Ying Han.

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Lin, H., Li, M., Zhan, Y. et al. Disrupted white matter functional connectivity in aMCI APOEε4 carriers: a resting-state study. Brain Imaging and Behavior 15, 1739–1747 (2021). https://doi.org/10.1007/s11682-020-00367-7

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