Abstract

INTRODUCTION: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.

METHODS: Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.

RESULTS: Higher Plasma NfL was associated with greater altered diffusion measures of select tracts.

DISCUSSION: Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.

HIGHLIGHTS: The onset of such WM changes in DS has not yet been widely studied.WM microstructural properties correlated with plasma neurofilament light chain (NfL).NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.

Document Type

Article

Publication Date

1-1-2024

Notes/Citation Information

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s). Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Digital Object Identifier (DOI)

https://doi.org/10.1002/dad2.70023

Funding Information

This work was sup- ported by the National Institutes of Health (Grants U19AG068054, U01AG051412, R01 NS026861, R01 NS114562, NS106384). The funding sources were not involved in the conduct of the research and/or the preparation of the article.

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