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.

Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome