Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities
Open accessAbstract
White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid 42 deposition (Aβ 42), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 ± 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ 42 (β = -0.001, p = 0.007) and NFL (β = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ 42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.
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Existing evidence from human studies strongly supports the relationship between raised NFL levels and WM microstructure damage.
“Existing evidence from human studies strongly support the relationship between raised NFL levels and WM microstructure damage (Moore et al., 2018, Osborn et al., 2018).”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Osborn et al., 2018
The Discussion (page unavailable) reports that higher CSF NFL was associated with greater white matter hyperintensities in older adults. This supports a relationship with white matter injury, but the study measured FLAIR-assessed hyperintensities, not white matter microstructure directly, and describes its cross-sectional findings as initial evidence rather than strong support. (LLM, conf=0.86)
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- Authors
- Osborn, K. E., Liu, D., Samuels, L. R., Moore, E. E., Cambronero, F. E., Acosta, L. M. Y., Bell, S. P., Babicz, M. A., Gordon, E. A., Pechman, K. R., Davis, L. T., Gifford, K. A., Hohman, T. J., Blennow, K., Zetterberg, H., & Jefferson, A. L.
- Affiliations
- Vanderbilt University Medical Center (US)
- University of Gothenburg (SE)
- Corresponding author
- Jefferson, Angela L.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 68
- Pages
- 18-25
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC6085839
- OpenAlex
- W2795444854
- Cited by
- 51
- References
- 52
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 9 · 2018: 4
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Vanderbilt University
- National Institutes of Health (1s10od023680-01, UL1TR000445, UL1TR002243)
- National Institute on Aging (R01AG056534, K24AG046373, K23AG030962, K23AG045966, K23AG048347, K01AG049164, F32AG058395, R01AG034962)
- National Institute of Mental Health (T32MH064913)
- National Institute of General Medical Sciences (T32GM007347, R25GM062459)
- National Institute of Neurological Disorders and Stroke (R01NS100980)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083211, K12HD043483)
- Topics
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- white matter hyperintensities, cerebrospinal fluid biomarkers, neurofilament light chain, axonal injury, hyperphosphorylated tau, total tau, neurodegeneration, amyloid deposition, older adults, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, Neurofilament Proteins, White Matter
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