Abstract
INTRODUCTION Down syndrome (DS) may be considered a genetic form of Alzheimer’s disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions.
METHODS We measured blood NF-L concentration in 100 adults with DS using Simoa NF-light® assays, and examined relationships with age, and cross-sectional and longitudinal dementia diagnosis.
RESULTS NF-L levels increased with age (Spearman’s rho = 0.789, p<0.001), with a steep increase after age 40, and were predictive of dementia status (p=0.022 adjusting for age, sex, and APOE4) but showed no relationship with longstanding epilepsy or premorbid ability. Baseline NF-L levels were associated with longitudinal dementia status.
DISCUSSION NF-L is a biomarker for neurodegeneration in DS, with potential for use in future clinical trials to prevent or delay dementia.
Systematic review The authors reviewed the literature using PubMed searches supplemented with our knowledge of pending papers in this research area. While blood NF-L has been associated with clinical features of progression in a number of neurodegenerative conditions, we have not identified any reports of NF-L associated with cognitive decline in DS, a genetic form of AD.
Interpretation Our findings demonstrate the potential utility of NF-L as a blood biomarker of neurodegeneration in DS, a population that may not be able to tolerate more invasive procedures such as neuroimaging and lumbar punctures to track progression.
Future directions The association between NF-L and other markers of longitudinal AD progression should be explored further in future work.
Author contributions
Conception and design of the study: AS, HZ; acquisition of data: AH, KM, JH, JG, DN, HZ; analysis of data: AS, CS; writing the manuscript: AS, CS; revising the manuscript for important intellectual content: all co-authors.
Footnotes
Conflicts of interest: AS has consulted for Ono pharmaceuticals, is an adviser to the UK Down Syndrome Association, and is an advisory board member of the LuMind Foundation (USA). HZ has served at advisory boards of Roche Diagnostics, Eli Lilly, and Teva, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg.
No other authors have any competing interests to declare.