. 2018 Apr 10;10(1):39.

doi: 10.1186/s13195-018-0367-x.

Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

Andre Strydom^{1

2

3}, Amanda Heslegrave⁴, Carla M Startin^{5

6

7}, Kin Y Mok^{7

4

8}, John Hardy^{7

4

9}, Jurgen Groet^{7

10}, Dean Nizetic^{7

10

11}, Henrik Zetterberg^{4

12

13}; LonDownS Consortium

Collaborators, Affiliations

Collaborators

LonDownS Consortium:
Andre Strydom, Elizabeth Fisher, Dean Nizetic, John Hardy, Victor Tybulewicz, Annette Karmiloff-Smith, Sarah Hamburg, Rosalyn Hithersay

Affiliations

¹ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK. andre.strydom@kcl.ac.uk.
² Division of Psychiatry, University College London, London, UK. andre.strydom@kcl.ac.uk.
³ The LonDownS Consortium, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, SE5 8AF, UK. andre.strydom@kcl.ac.uk.
⁴ Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
⁵ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK.
⁶ Division of Psychiatry, University College London, London, UK.
⁷ The LonDownS Consortium, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, SE5 8AF, UK.
⁸ Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, Hong Kong, Special Administrative Region of China.
⁹ Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.
¹⁰ Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
¹¹ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
¹² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
¹³ UK Dementia Research Institute at UCL, London, UK.

PMID: 29631614
PMCID: PMC5891918
DOI: 10.1186/s13195-018-0367-x

Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

Andre Strydom et al. Alzheimers Res Ther. 2018.

. 2018 Apr 10;10(1):39.

doi: 10.1186/s13195-018-0367-x.

Authors

Collaborators

LonDownS Consortium:
Andre Strydom, Elizabeth Fisher, Dean Nizetic, John Hardy, Victor Tybulewicz, Annette Karmiloff-Smith, Sarah Hamburg, Rosalyn Hithersay

Affiliations

¹ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK. andre.strydom@kcl.ac.uk.
² Division of Psychiatry, University College London, London, UK. andre.strydom@kcl.ac.uk.
³ The LonDownS Consortium, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, SE5 8AF, UK. andre.strydom@kcl.ac.uk.
⁴ Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
⁵ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK.
⁶ Division of Psychiatry, University College London, London, UK.
⁷ The LonDownS Consortium, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, SE5 8AF, UK.
⁸ Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, Hong Kong, Special Administrative Region of China.
⁹ Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.
¹⁰ Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
¹¹ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
¹² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
¹³ UK Dementia Research Institute at UCL, London, UK.

PMID: 29631614
PMCID: PMC5891918
DOI: 10.1186/s13195-018-0367-x

Abstract

Background: 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 concentrations in 100 adults with DS using Simoa NF-light® assays, and we examined relationships with age as well as cross-sectional and longitudinal dementia diagnosis.

Results: NF-L concentrations increased with age (Spearman's rho = 0.789, p < 0.001), with a steep increase after age 40, and they were predictive of dementia status (p = 0.022 adjusting for age, sex, and APOE4), but they showed no relationship with long-standing epilepsy or premorbid ability. Baseline NF-L concentrations were associated with longitudinal dementia status.

Conclusions: NF-L is a biomarker for neurodegeneration in DS with potential for use in future clinical trials to prevent or delay dementia.

Keywords: Alzheimer’s disease; Biomarker; Dementia; Down syndrome; Neurofilament light.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The North West Wales National Health Service (NHS) Research Ethics Committee provided ethical approval for a longitudinal study of cognitive ability and dementia in DS (13/WA/0194). For those with decision-making capacity, written consent was obtained, whereas for those who did not have decision-making capacity, a consultee indicated their agreement to participation.

Competing interests

AS has consulted for Ono Pharmaceutical Co., is an adviser to the UK Down Syndrome Association, and is an advisory board member of the LuMind Research Down Syndrome Foundation (USA). HZ has served on advisory boards of Roche Diagnostics, Eli Lilly, and Teva and is a cofounder of Brain Biomarker Solutions with Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. The other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Neurofilament light (NF-L) concentration by age and dementia status of individuals with Down syndrome

See this image and copyright information in PMC

References

1. Wiseman FK, Al-Janabi T, Hardy J, Karmiloff-Smith A, Nizetic D, Tybulewicz VL, Fisher EM, Strydom A. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci. 2015;16(9):564–574. doi: 10.1038/nrn3983. - DOI - PMC - PubMed
1. McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res. 2017;61(9):843–852. doi: 10.1111/jir.12390. - DOI - PubMed
1. Sinai A, Mokrysz C, Bernal J, Bohnen I, Bonell S, Courtenay K, Dodd K, Gazizova D, Hassiotis A, Hillier R, et al. Predictors of age of diagnosis and survival of Alzheimer’s disease in down syndrome. J Alzheimers Dis. 2018;61(2):717–728. doi: 10.3233/JAD-170624. - DOI - PMC - PubMed
1. Zis P, Strydom A. Clinical aspects and biomarkers of Alzheimer’s disease in Down syndrome. Free Radic Biol Med. 2018;114:3–9. doi: 10.1016/j.freeradbiomed.2017.08.024. - DOI - PMC - PubMed
1. Zetterberg H. Neurofilament light: a dynamic cross-disease fluid biomarker for neurodegeneration. Neuron. 2016;91(1):1–3. doi: 10.1016/j.neuron.2016.06.030. - DOI - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

Collaborators

Affiliations

Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases