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

Article type: Research Article

Authors: Rafii, Michael S.^{a; *} | Donohue, Michael C.^a | Matthews, Dawn C.^b | Muranevici, Gabriela^a | Ness, Seth^c | O’Bryant, Sid E.^d | Rissman, Robert A.^{e; f}

Affiliations: [a] Alzheimer’s Therapeutic Research Institute, Keck School of Medicine of USC, Los Angeles, CA, USA | [b] ADM Diagnostics, Inc., Northbrook, IL, USA | [c] Janssen Research, Titusville, NJ, USA | [d] University of North Texas Health Sciences Center, Fort Worth, TX, USA | [e] Department of Neurosciences, University of California, San Diego, San Diego, CA, USA | [f] VA San Diego Healthcare System, San Diego, CA, USA

Correspondence: [*] Correspondence to: Michael S. Rafii, MD, PhD, 9860 Mesa Rim Road, San Diego, CA 92121, USA. Tel.: +1 858 964 0638; E-mail: mrafii@usc.edu.

Abstract: 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.

Keywords: Alzheimer’s disease, amyloid, biomarkers, blood, Down syndrome, neurofilament light, plasma, tau

DOI: 10.3233/JAD-190322

Journal: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 131-138, 2019