Association of Serum Neurofilament Light and Glial Fibrillary Acidic Protein with Cerebral Small Vessel Disease in Nondemented Middle-to-Old Aged Population.

Neurofilament light chain (NfL) and brain glial fibrillary acidic protein (GFAP) are promising markers for cerebral vascular damage. We aimed to evaluate if increased serum NfL and GFAP were associated with cerebral small vessel disease (CSVD) markers among the nondemented middle-to-old aged population. We included participants from the Shunyi Study who had serum NfL and GFAP measurements. Cerebral microbleeds (CMBs), lacunes, perivascular space (PVS) white matter hyperintensities volume (WMHV), and brain parenchymal fraction (BPF) were measured. Cross-sectional and longitudinal associations between CSVD imaging markers and NfL levels were evaluated using multivariable-adjusted models. We included 848 nondemented participants (mean age: 55.5 ± 8.7 years) cross-sectionaly. Among these participants, 603 underwent longitudinal analysis, with an average follow-up time of 5.59 years (range: 4.34-7.20 years). Serum NfL was positively associated with baseline lacunes (OR = 1.40, 95% CI: 1.12-1.75) and WMHV (P < 0.001). GFAP was positively associated with WMHV (P = 0.016), while the association disappeared when including NfL simultaneously in the model. CMBs, PVS, and BPF were not associated with the biomarkers. Logitudinally, baseline NfL was significantly higher among participants with incident lacunes (OR: 1.44, 95% CI: 1.07-1.92); however, this association was attenuated and lost statistical significance after further adjustment for baseline lacune. Increased serum NfL appears to be indicative of lacunes and also the progression of lacunes among middle-to-old-age population. The association between serum NfL and CSVD image markers was less pronounced in the middle-to-old-age population than in the elderly, while GFAP did not prove to be a valuable CSVD biomarker. KEY POINTS: The association between serum NfL and CSVD was less pronounced in the middle-to-old-age population than in the elderly. Serum NfL was positively associated with lacunes (OR = 1.40, 95% CI: 1.12-1.75) and WMHV (P < 0.001). Baseline serum NfL was associated with a 44% increased risk of incident lacunes over a 5.59-year follow-up, but was attenuated after controlling for baseline lacune. Other CVSD markers, including CMBs, PVS, and BPF, showed no association with either NfL or GFAP.