| Title: | Association of Plasma GFAP and NfL in Middle-Aged Adults With MRI Markers of Cerebral Small Vessel Disease Later in Life |
| Journal: | Neurology |
| Published: | 29 Dec 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41461058/ |
| DOI: | https://doi.org/10.1212/wnl.0000000000214481 |
Publication 16953
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Abstract
BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (cSVD) is a major contributor to stroke and dementia, often beginning decades before clinical symptoms appear. While MRI markers offer critical insight into cSVD burden, blood-based biomarkers may offer a more accessible complement to neuroimaging. We investigated whether plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are associated with MRI markers of cSVD in middle-aged adults and whether they are associated with longitudinal progression.</p>
METHODS: We conducted a retrospective analysis of prospectively collected data from the UK Biobank cohort. Participants aged 40-60 years at baseline (2006-2010) with plasma biomarker measurements and follow-up MRI scans (2014-2019) were included. Individuals with prevalent neurologic conditions were excluded. We assessed 3 MRI markers of cSVD: white matter hyperintensities (WMHs), fractional anisotropy (FA), and mean diffusivity (MD). Three analytical approaches were used: associations between baseline biomarkers and future MRI markers, associations between baseline biomarkers and longitudinal MRI changes, and correlations between longitudinal biomarker and MRI changes. Robust regression models were adjusted for age, sex, and cerebrovascular risk factors.</p>
RESULTS: Among 5,270 participants (mean age 54.2 ± 7.8 years; 53.4% female), higher baseline GFAP levels were significantly associated with all 3 MRI cSVD markers-WMH volume (β = 0.06, 95% CI 0.01-0.10, p = 0.014), FA (β = 0.08, 95% CI 0.03-0.13, p = 0.001), and MD (β = 0.14, 95% CI 0.09-0.18, p < 0.001)-after a follow-up of 9 years. Among 1,317 participants with longitudinal MRI data, baseline GFAP was associated with progression of FA (β = 0.012, 95% CI 0.001-0.023, p = 0.033) and MD (β = 0.020, 95% CI 0.003-0.038, p = 0.025) over 3 years. NfL was not significantly associated with any MRI cSVD marker. Longitudinal changes in both biomarkers showed no significant associations with concurrent MRI progression.</p>
DISCUSSION: Plasma GFAP levels were associated with subsequent changes in white matter integrity among middle-aged adults, suggesting potential utility as an early indicator of cSVD vulnerability. These associations, observed nearly a decade after biomarker measurement, highlight GFAP's potential for long-term risk stratification. Blood-based biomarkers may support earlier identification of individuals at heightened risk of cSVD, enabling preventive strategies when interventions may be most effective.</p>
14 Keywords
- Adult
- Biomarkers
- Cerebral Small Vessel Diseases
- Disease Progression
- Female
- Glial Fibrillary Acidic Protein
- Humans
- Longitudinal Studies
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Neurofilament Proteins
- Retrospective Studies
- White Matter
14 Authors
- Savvina Prapiadou
- Benjamin Y Q Tan
- Tamara N Kimball
- Samantha Mora
- Reinier W P Tack
- Devanshi Choksi
- Marie-Gabrielle Duperron
- Jasper R Senff
- Evy M Reinders
- Christina Kourkoulis
- Sanjula Dhillon Singh
- Nirupama Yechoor
- Jonathan Rosand
- Christopher D Anderson
1 Application
| Application ID | Title |
|---|---|
| 36993 | Identification of genetic components underlying cerebrovascular diseases and their related outcomes |
Enabling scientific discoveries that improve human health