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Cerebrospinal Fluid Biomarkers in Huntington’s Disease

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Biomarkers for Huntington's Disease

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion mutation in the HTT gene that leads to progressive loss of neurons particularly in the striatum and cortex. Despite significant advances in our understanding of the molecular and cellular mechanisms underlying HD, there is still no cure or effective treatment for this disorder. In recent years, there has been growing interest in identifying HD biomarkers that could aid in the diagnosis, monitoring, and treatment of this disorder. Cerebrospinal fluid (CSF) has been increasingly used as a source of biomarkers for neurological diseases. This book chapter provides an overview of the current state of knowledge regarding CSF biomarkers in HD. It starts with a brief historical introduction to the study of CSF in disease, then introduces Huntington’s disease and some of the challenges associated with the diagnosis and management of this disorder. This chapter then reviews the different classes of CSF biomarkers that have been studied in HD, including neurotransmitters, amino acids, proteins, metabolites, metals, and microRNAs. CSF levels of mutant huntingtin and neurofilament light chain are leading potential biomarkers and are being qualified for clinical use in ongoing HD clinical trials of huntingtin-lowering therapies.

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Abbreviations

DOPAC:

3,4-dihydroxyphenylacetic acid

BDNF:

Brain derived neurotrophic factor

CSF:

Cerebrospinal fluid

DA:

Dopamine

GABA:

Gamma-aminobutyric acid

HVA:

Homovanilic acid

HTT:

Huntingtin protein

HD:

Huntington’s disease

LP:

Lumbar puncture

MSNs:

Medium spiny projection neurons

mHTT:

Mutant huntingtin protein

GGEL:

NE-(omega-1-glutamyl)-1-LYSINE

NfL:

Neurofilament light chain

NMDA:

N-methyl D-aspartate

PDYN :

Prodynorphin

PENK :

Proenkephalin

TREM2:

Triggering receptor expressed on myeloid cells-2

TFC:

Total Functional Capacity

TMS:

Total Motor Score

UHDRS:

Unified Huntington’s Disease Rating Scale

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Authors and Affiliations

  1. Center for Brain Health, University of British Columbia Hospital, Vancouver, BC, Canada

    Fabricio Pio & Blair R. Leavitt

  2. Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics and Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada

    Blair R. Leavitt

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  1. Fabricio Pio
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Correspondence to Blair R. Leavitt .

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  1. Department of Neurobiology and Behavior, University of California, Irvine, CA, USA

    Elizabeth A. Thomas

  2. Department of Neurosciences, University of California, San Diego, CA, USA

    Georgia M. Parkin

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Pio, F., Leavitt, B.R. (2023). Cerebrospinal Fluid Biomarkers in Huntington’s Disease. In: Thomas, E.A., Parkin, G.M. (eds) Biomarkers for Huntington's Disease. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-031-32815-2_2

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