The Updated Development of Blood-based Biomarkers for Huntington's Disease

Overview

Journal J Neurol

Specialty Neurology

Date 2023 Jan 24

PMID 36692635

Authors

Sirui Zhang

Yangfan Cheng

Huifang Shang

Affiliations

Soon will be listed here.

Abstract

Huntington's disease is a progressive neurodegenerative disease caused by mutation of the huntingtin (HTT) gene. The identification of mutation carriers before symptom onset provides an opportunity to intervene in the early stage of the disease course. Optimal biomarkers are of great value to reflect neuropathological and clinical progression and are sensitive to potential disease-modifying treatments. Blood-based biomarkers have the merits of minimal invasiveness, low cost, easy accessibility and safety. In this review, we summarized the updated development of blood-based biomarkers for HD from six aspects, including neuronal injuries, oxidative stress, endocrine functions, immune reactions, metabolism and differentially expressed miRNAs. The blood-based biomarkers presented and discussed in this review were close to clinical applicability and might facilitate clinical design as surrogate endpoints. Exploration and validation of robust blood-based biomarkers require further standard and systemic study design in the future.

Citing Articles

Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.

Aqel S, Ahmad J, Saleh I, Fathima A, Al Thani A, Mohamed W Biology (Basel). 2025; 14(2).

PMID: 40001897 PMC: 11852324. DOI: 10.3390/biology14020129.

Serum metabolomic signatures of patients with rare neurogenetic diseases: an insight into potential biomarkers and treatment targets.

Wijekoon N, Gonawala L, Ratnayake P, Sirisena D, Gunasekara H, Dissanayake A Front Mol Neurosci. 2025; 17:1482999.

PMID: 39866907 PMC: 11759312. DOI: 10.3389/fnmol.2024.1482999.

Inflammasomes in neurodegenerative diseases.

Wang Q, Yang S, Zhang X, Zhang S, Chen L, Wang W Transl Neurodegener. 2024; 13(1):65.

PMID: 39710713 PMC: 11665095. DOI: 10.1186/s40035-024-00459-0.

Investigating the Interplay between Cardiovascular and Neurodegenerative Disease.

Cousineau J, Dawe A, Alpaugh M Biology (Basel). 2024; 13(10).

PMID: 39452073 PMC: 11505144. DOI: 10.3390/biology13100764.

Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases.

Issa S, Fayoud H, Shaimardanova A, Sufianov A, Sufianova G, Solovyeva V Biomedicines. 2024; 12(8).

PMID: 39200370 PMC: 11351319. DOI: 10.3390/biomedicines12081906.

References

Ross C, Aylward E, Wild E, Langbehn D, Long J, Warner J . Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014; 10(4):204-16. DOI: 10.1038/nrneurol.2014.24. View

Bates G, Dorsey R, Gusella J, Hayden M, Kay C, Leavitt B . Huntington disease. Nat Rev Dis Primers. 2016; 1:15005. DOI: 10.1038/nrdp.2015.5. View

Przybyl L, Wozna-Wysocka M, Kozlowska E, Fiszer A . What, When and How to Measure-Peripheral Biomarkers in Therapy of Huntington's Disease. Int J Mol Sci. 2021; 22(4). PMC: 7913877. DOI: 10.3390/ijms22041561. View

Evans S, Douglas I, Rawlins M, Wexler N, Tabrizi S, Smeeth L . Prevalence of adult Huntington's disease in the UK based on diagnoses recorded in general practice records. J Neurol Neurosurg Psychiatry. 2013; 84(10):1156-60. PMC: 3786631. DOI: 10.1136/jnnp-2012-304636. View

Fisher E, Hayden M . Multisource ascertainment of Huntington disease in Canada: prevalence and population at risk. Mov Disord. 2013; 29(1):105-14. DOI: 10.1002/mds.25717. View

Tabrizi S, Flower M, Ross C, Wild E . Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol. 2020; 16(10):529-546. DOI: 10.1038/s41582-020-0389-4. View

Rubinsztein D, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman J . Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet. 1996; 59(1):16-22. PMC: 1915122. View

Tabrizi S, Schobel S, Gantman E, Mansbach A, Borowsky B, Konstantinova P . A biological classification of Huntington's disease: the Integrated Staging System. Lancet Neurol. 2022; 21(7):632-644. DOI: 10.1016/S1474-4422(22)00120-X. View

Tabrizi S, Ghosh R, Leavitt B . Huntingtin Lowering Strategies for Disease Modification in Huntington's Disease. Neuron. 2019; 102(4):899. DOI: 10.1016/j.neuron.2019.05.001. View

10.

Tabrizi S, Estevez-Fraga C, van Roon-Mom W, Flower M, Scahill R, Wild E . Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities. Lancet Neurol. 2022; 21(7):645-658. PMC: 7613206. DOI: 10.1016/S1474-4422(22)00121-1. View

11.

Cheng Y, Chen Y, Shang H . Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis. Transl Neurodegener. 2021; 10(1):3. PMC: 7792103. DOI: 10.1186/s40035-020-00228-9. View

12.

Zeun P, Scahill R, Tabrizi S, Wild E . Fluid and imaging biomarkers for Huntington's disease. Mol Cell Neurosci. 2019; 97:67-80. DOI: 10.1016/j.mcn.2019.02.004. View

13.

Weir D, Sturrock A, Leavitt B . Development of biomarkers for Huntington's disease. Lancet Neurol. 2011; 10(6):573-90. DOI: 10.1016/S1474-4422(11)70070-9. View

14.

Paulsen J, Langbehn D, Stout J, Aylward E, Ross C, Nance M . Detection of Huntington's disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry. 2007; 79(8):874-80. PMC: 2569211. DOI: 10.1136/jnnp.2007.128728. View

15.

Aylward E, Liu D, Nopoulos P, Ross C, Pierson R, Mills J . Striatal volume contributes to the prediction of onset of Huntington disease in incident cases. Biol Psychiatry. 2011; 71(9):822-8. PMC: 3237730. DOI: 10.1016/j.biopsych.2011.07.030. View

16.

Jurgens C, van de Wiel L, van Es A, Grimbergen Y, Witjes-Ane M, van der Grond J . Basal ganglia volume and clinical correlates in 'preclinical' Huntington's disease. J Neurol. 2009; 255(11):1785-91. DOI: 10.1007/s00415-008-0050-4. View

17.

Fazio P, Paucar M, Svenningsson P, Varrone A . Novel Imaging Biomarkers for Huntington's Disease and Other Hereditary Choreas. Curr Neurol Neurosci Rep. 2018; 18(12):85. PMC: 6182636. DOI: 10.1007/s11910-018-0890-y. View

18.

Paulsen J, Long J, Johnson H, Aylward E, Ross C, Williams J . Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study. Front Aging Neurosci. 2014; 6:78. PMC: 4000999. DOI: 10.3389/fnagi.2014.00078. View

19.

Tabrizi S, Scahill R, Owen G, Durr A, Leavitt B, Roos R . Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol. 2013; 12(7):637-49. DOI: 10.1016/S1474-4422(13)70088-7. View

20.

Hensman Moss D, Pardinas A, Langbehn D, Lo K, Leavitt B, Roos R . Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study. Lancet Neurol. 2017; 16(9):701-711. DOI: 10.1016/S1474-4422(17)30161-8. View