Plasma Neurofilament Light and Alzheimer's Disease Biomarkers in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI)

Background: Adults with Down syndrome (DS) are at very high risk for Alzheimer's disease (AD). Neurofilament light (NF-L) has emerged as a potential blood-based biomarker of neurodegeneration due to AD.

Objective: To understand the relationship between plasma NF-L with age, brain amyloid, and tau pathology, neurodegeneration as well as cognitive and functional performance.

Methods: We analyzed imaging data as well as cognitive measures in relation to plasma NF-L in adults with DS, ages 30 to 60 who were enrolled in the Down Syndrome Biomarker Initiative.

Results: We found significant correlations between NF-L plasma concentrations and amyloid pathology (r = 0.73, p = 0.007, pa = 0.041) and significant inverse correlations with regional glucose metabolism in 5 of 6 regions examined, which were Anterior cingulate (r = -0.55, p = 0.067, pa = 0.067), Posterior cingulate r = -0.90, p < 0.001, pa < 0.001), Lateral Temporal (r = -0.78, p = 0.004, pa = 0.012), Frontal cortex (r = -0.90, p < 0.001, p pa < 0.001), Parietal cortex (r = -0.82, p = 0.002, pa = 0.008), Precuneus (r = -0.73, pa = 0.010, pa = 0.020), and with hippocampal volume (r = -0.52, p = 0.084, pa = 0.084); and an inverse correlation with direct measures of cognition: CAMCOG (r = -0.66 p = 0.022, pa = 0.066) and positive correlation with CANTAB Paired Associates Learning (PAL) error rate (r = 0.68, p = 0.015, pa = 0.060). Finally, we found inverse relationships with informant-based functional measures (r = -0.57, p = 0.059, pa = 0.084) and OMQ-PF (r = -0.74, p = 0.008, pa = 0.041).

Conclusion: Plasma NF-L is associated with progressive neurodegeneration as well as with declines in cognitive and functional measures in adults with DS.