Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease
Autor: | Schultz, Stephanie A, Strain, Jeremy F, Berman, Sarah B, Brickman, Adam M, Cash, David M, Chhatwal, Jasmeer, Cruchaga, Carlos, Ewers, Michael, Fox, Nick N, Ghetti, Bernardino, Goate, Alison, Graff-Radford, Neill R, Adedokun, Adedamola, Hassenstab, Jason J, Hornbeck, Russ, Jack, Clifford, Johnson, Keith, Joseph-Mathurin, Nelly, Karch, Celeste M, Koeppe, Robert A, Lee, Athene K W, Levin, Johannes, Masters, Colin, Wang, Qing, McDade, Eric, Perrin, Richard J, Rowe, Christopher C, Salloway, Stephen, Saykin, Andrew J, Sperling, Reisa, Su, Yi, Villemagne, Victor L, Vöglein, Jonathan, Weiner, Michael, Preische, Oliver, Xiong, Chengjie, Fagan, Anne M, Morris, John C, Bateman, Randall J, Benzinger, Tammie L S, Jucker, Mathias, Gordon, Brian A, Network, Dominantly Inherited Alzheimer, Kuhle, Jens, Flores, Shaney, Keefe, Sarah, Dincer, Aylin, Ances, Beau M |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Blood-based biomarkers Neuroimaging Neurofilament diagnostic imaging [White Matter] Article lcsh:RC321-571 White matter 03 medical and health sciences blood [Alzheimer Disease] 0302 clinical medicine Cerebrospinal fluid Alzheimer Disease ddc:570 Fractional anisotropy medicine Humans Neurodegeneration lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry diagnostic imaging [Brain] blood [Biomarkers] business.industry Brain Alzheimer's disease Middle Aged medicine.disease Hyperintensity 030104 developmental biology medicine.anatomical_structure Diffusion Tensor Imaging Neurology Biomarker (medicine) Female business diagnostic imaging [Alzheimer Disease] 030217 neurology & neurosurgery Biomarkers Diffusion MRI |
Zdroj: | Neurobiology of Disease Neurobiology of disease 142, 104960-(2020). doi:10.1016/j.nbd.2020.104960 Neurobiology of Disease, Vol 142, Iss, Pp 104960-(2020) |
ISSN: | 1095-953X 0969-9961 |
Popis: | Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases. Highlights • Serum NfL levels reflect white matter integrity in autosomal dominant Alzheimer disease. • Associations between NfL and white matter imaging are present throughout all brain regions. • Longitudinal white matter alterations are associated with changes in blood NfL. • Results improve interpretability of NfL as a marker of brain integrity. |
Databáze: | OpenAIRE |
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