Plasma Neurofilament Light Concentration Is Associated with Diffusion-Tensor MRI-Based Measures of Neurodegeneration in Early Parkinson’s Disease

Article type: Research Article

Authors: Welton, Thomas^{a; b; c} | Tan, Yi Jayne^{a; c} | Saffari, Seyed Ehsan^{a; c; d} | Ng, Samuel Y.E.^{a; c} | Chia, Nicole S.Y.^{a; c} | Yong, Alisa C.W.^{a; c} | Choi, Xinyi^{c; e} | Heng, Dede Liana^{c; e} | Shih, Yao-Chia^{f; g} | Hartono, Septian^{b; c; e} | Lee, Weiling^h | Xu, Zheyu^{a; c} | Tay, Kay Yaw^{a; c} | Au, Wing Lok^{a; c} | Tan, Eng-King^{a; c; e} | Chan, Ling Ling^{c; f; h; i} | Ng, Adeline S.L.^{a; c; i; †} | Tan, Louis C.S.^{a; c; *; †}

Affiliations: [a] Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore | [b] Neuroscience Academic Clinical Program, Duke-NUS Medical School, Singapore | [c] Parkinson Disease and Movement Disorders Centre, Parkinson Foundation Center of Excellence, National Neuroscience Institute, Singapore, Tan Tock Seng Hospital, Singapore | [d] Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore | [e] Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore | [f] Radiological Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore | [g] Graduate Institute of Medicine, Yuan Ze University, Taoyuan City, Taiwan | [h] Department of Diagnostic Radiology, Singapore General Hospital, Singapore | [i] Neuroscience and Behavioural Disorders Program, Duke-NUS Medical School, Singapore

Correspondence: [*] Correspondence to: Prof. Louis C.S. Tan, Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433. Tel.: +65 6357 7153; E-mail: [email protected].

Note: [†] Joint senior authors.

Abstract: Background:Neurofilament light is a marker of axonal degeneration, whose measurement from peripheral blood was recently made possible by new assays. Objective:We aimed to determine whether plasma neurofilament light chain (NfL) concentration reflects brain white matter integrity in patients with early Parkinson’s disease (PD). Methods:137 early PD patients and 51 healthy controls were included. Plasma NfL levels were measured using ultrasensitive single molecule array. 3T MRI including diffusion tensor imaging was acquired for voxelwise analysis of association between NfL and both fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts and subcortical nuclei. Results:A pattern of brain microstructural changes consistent with neurodegeneration was associated with increased plasma NfL in most of the frontal lobe and right internal capsule, with decreased FA and increased MD. The same clusters were also associated with poorer global cognition. A significant cluster in the left putamen was associated with increased NfL, with a significantly greater effect in PD than controls. Conclusion:Plasma NfL may be associated with brain microstructure, as measured using diffusion tensor imaging, in patients with early PD. Higher plasma NfL was associated with a frontal pattern of neurodegeneration that also correlates with cognitive performance in our cohort. This may support a future role for plasma NfL as an accessible biomarker for neurodegeneration and cognitive dysfunction in PD.

Keywords: diffusion MRI, neurodegeneration, neurofilament, Parkinson’s disease, single molecule array, TBSS

DOI: 10.3233/JPD-223414

Journal: Journal of Parkinson's Disease, vol. 12, no. 7, pp. 2135-2146, 2022