Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

Strydom, A.; Heslegrave, A.; Startin, C. M.; Mok, K. Y.; Hardy, J.; Groet, J.; Nizetic, D.; The LonDownS consortium,; Zetterberg, H.

doi:10.1101/281139

bioRxiv · 10.1101/281139

Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

Strydom, A.·Heslegrave, A.·Startin, C. M.·Mok, K. Y.·Hardy, J.·Groet, J.·Nizetic, D.·The LonDownS consortium,·Zetterberg, H.

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Abstract

INTRODUCTIONDown syndrome (DS) may be considered a genetic form of Alzheimers 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.\n\nMETHODSWe measured blood NF-L concentration in 100 adults with DS using Simoa NF-light(R) assays, and examined relationships with age, and cross-sectional and longitudinal dementia diagnosis.\n\nRESULTSNF-L levels increased with age (Spearmans 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.\n\nDISCUSSIONNF-L is a biomarker for neurodegeneration in DS, with potential for use in future clinical trials to prevent or delay dementia.\n\nResearch in contextO_ST_ABSSystematic reviewC_ST_ABSThe 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.\n\nInterpretationOur 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.\n\nFuture directionsThe association between NF-L and other markers of longitudinal AD progression should be explored further in future work.

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Strydom, A., Heslegrave, A., Startin, C. M., Mok, K. Y., Hardy, J., Groet, J., Nizetic, D., The LonDownS consortium,, Zetterberg, H.. 2018-03-13. Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome. https://doi.org/10.1101/281139

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