Periventricular diffusion gradient of normal-appearing white matter and its transcriptional signatures in normal aging and multiple neurological diseases

Author:

Zhuo Zhizheng1,Tian Decai1,Duan Yunyun2,Li Runzhi3,Bai Yutong4,Shi Yulu3,Xu Xiaolu1,Xu Siyao3,Lv Shan3,Cao Guanmei5,Hu Geli6,Xu Jun1,Zhang Jianguo1,Shi Fu-Dong7ORCID,Chard Declan8ORCID,Barkhof Frederik9ORCID,Haller Sven10,Zhang Xinghu11,Liu Yaou12

Affiliation:

1. Beijing Tiantan Hospital, Capital Medical University

2. Department of Radiology, Xuanwu Hospital, Capital Medical University

3. Beijing Tiantan Hospital, Capital Medical University.

4. Beijing Tian Tan Hospital

5. Xuanwu Hospital, Capital Medical University

6. Philips Healthcare

7. Beijing Tiantan Hospital

8. NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, UK.

9. University College London

10. University of Geneva

11. Tiantan Hospital, Capital Medical University

12. Department of Radiology, Beijing Tiantan Hospital, Capital Medical University

Abstract

Abstract Abnormal periventricular gradient of normal-appearing white matter (NAWM) is a common WM signature of aging and multiple neurological diseases. Here, we investigated the periventricular gradient of NAWM and its association with brain-wide gene expression in middle-aged and elderly participants with Alzheimer's disease, Parkinson's disease, cerebral small vessel disease, and multiple sclerosis compared to young healthy controls (HC), using diffusion magnetic resonance imaging data. Using the normalized neurite density and orientation dispersion indices, we observed the abnormal periventricular diffusion gradients in elderly HC and those with diseases, and the gradients correlated with brain volumes and cognitive performances. Using gene expression data, we observed the periventricular diffusion gradient in a normal aging population and patients with multiple neurological disorders associated with transcriptional changes in endothelial, synaptic, and immunologic functions. We determined a periventricular diffusion gradient of NAWM in normal aging and multiple neurological diseases and revealed its possible transcriptional signatures.

Publisher

Research Square Platform LLC

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