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Comparative Study
. 2025 Jan 23;272(2):158.
doi: 10.1007/s00415-024-12785-4.

Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease

Alison R Bamford  1   2 , Georgia M Parkin  3 , Jody Corey-Bloom  4 , Elizabeth A Thomas  5   6   7
Affiliations
Comparative Study

Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease

Alison R Bamford et al. J Neurol. .

Abstract

Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays. In addition, salivary levels of NfL, t-tau, and GFAP were quantified from a larger cohort (n = 95). We found both positive and negative correlations in the levels of these biomarkers among different biofluids. Most notably, in contrast to the significant positive correlations observed between CSF and plasma levels for NfL and GFAP, we detected significant negative correlations between the CSF and saliva levels of NfL and GFAP. With regard to clinical measures, both plasma and CSF levels of NfL were significantly positively correlated with Total Motor Score and chorea, whereas saliva levels of NfL showed significant correlations in the opposite direction. Additional correlations between salivary biomarkers with clinical data, adjusting for age, sex and CAG repeat length, confirmed that salivary NfL was significantly negatively associated with chorea scores in manifest HD, but not premanifest (PM), individuals. In contrast, salivary t-tau was positively associated with measures of cognition in PM participants. These findings suggest that salivary levels of NfL and t-tau proteins may exemplify non-invasive biomarkers for disease symptoms at different stages of illness. Further, these findings highlight the notion that different forms of disease proteins exist in different biological fluids.

Keywords: Biomarker; Neurodegeneration; Neurodegenerative; Neurofilament; Saliva; Tau.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethical approval: This study was approved by the University of California, San Diego (UCSD) Institutional Review Board, in accordance with the requirements of the Code of Federal Regulations on the Protection of Human Subjects. Informed consent: All participants provided their written informed consent to participate in this study.

Figures

Fig. 1
Fig. 1
Correlation of NfL, GFAP, t-tau, and YKL-40 across plasma, saliva, and CSF biofluids in Cohort 1. Unadjusted Spearman correlations are shown with the indicated correlation coefficients (rho, r) and p values for those correlations that were statistically significant. Data points only reflect values that were above the detection limit of the assay. NfL neurofilament light; GFAP glial fibrillary acidic protein
Fig. 2
Fig. 2
Correlation matrix of neurodegeneration biomarkers across CSF, plasma, and saliva. Correlation matrix reflects unadjusted Spearman correlation analysis. Associated p values for these correlations are shown in Table S2. NfL neurofilament light; GFAP glial fibrillary acidic protein
Fig. 3
Fig. 3
Correlations between plasma and salivary levels of NfL in HD mutation carriers (a) and normal controls (b). Spearman correlation analysis was carried out on gene-positive (PM plus HD) individuals (n = 68) and normal controls (n = 20). Data points only reflect values that were above the detection limit of the assay
Fig. 4
Fig. 4
Group-wise comparisons of salivary levels of NfL (a), GFAP (b), and t-tau (c) across different diagnostic groups. Statistical comparisons reflect ANCOVA adjusting for age across normal control (NC), premanifest (PM) and HD diagnoses. Asterisks reflect post hoc comparisons **, p < 0.01
See this image and copyright information in PMC

References

    1. Huntington Disease Collaborative Research Group D (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s disease collaborative research group. Cell 72(6):971–983 - PubMed
    1. Wexler NS (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc Natl Acad Sci USA 101(10):3498–3503 - PMC - PubMed
    1. Andresen JM, Gayán J, Djoussé L, Roberts S, Brocklebank D, Cherny SS, US‐Venezuela Collaborative Research Group HD MAPS, Collaborative Research Group et al (2007) The relationship between CAG repeat length and age of onset differs for Huntington’s disease patients with juvenile onset or adult onset. Ann Hum Genet 71(3):295–301 - PubMed
    1. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F et al (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington’s disease. Nat Genet 4(4):398–403 - PubMed
    1. Arrasate M, Finkbeiner S (2012) Protein aggregates in Huntington’s disease. Exp Neurol 238(1):1–11 - PMC - PubMed

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