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.
| Original language | English |
|---|---|
| Article number | e70023 |
| Journal | Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring |
| Volume | 16 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 1 2024 |
Bibliographical note
Publisher Copyright:© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Funding
The authors are grateful to the individuals who participated in this study and their caregivers who so generously contributed their time and energy to this project and without whom it would not have been possible. The authors also appreciate the efforts of the study teams who helped recruit and assess participants for this study, including Margaret Pulsifer, Sharon Krinsky‐McHale, Christy Hom, Courtney Jordan, Eric Doran, Nusrat Jahan, Kelsey Shelofsky, Gabriela Leka, Gianna Acosta, Eric Doran, Deborah Pang, Tracy Listwan, Cynthia Kovacs. The authors wish to thank Dr. Julie Price for her contributions. The authors thank Howard Andrews for all of his support and his contributions to the curation and maintenance of the study database. The authors also wish to thank Drs. Nicole Schupf, Ira Lott, Wayne Silverman, Ben Handen, Elizabeth Head, Mark Mapstone, and Brad Christian for their encouragement and support of this work. This work was supported 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.
| Funders | Funder number |
|---|---|
| National Institutes of Health (NIH) | NS106384, R01 NS114562, R01 NS026861, U01AG051412, U19AG068054 |
| National Institutes of Health (NIH) |
Keywords
- Alzheimer's disease
- Down syndrome
- diffusion weighted imaging
- white matter microstructural integrity
ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health
