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Molecular neurobiology
Jul, 2023;60 (7): 3873-3882.

Ganglioside-focused Glycan Array Reveals Abnormal Anti-GD1b Auto-antibody in Plasma of Preclinical Huntington's Disease.

Tien-Wei Lin, Jung-Kai Chang, Yih-Ru Wu, Tsung-Hsien Sun, Yang-Yu Cheng, Chien-Tai Ren, Mei-Hung Pan, Jin-Lin Wu, Kuo-Hsuan Chang, Hwai-I Yang, Chiung-Mei Chen, Chung-Yi Wu, Yun-Ru Chen
Author Information
  1. Tien-Wei Lin: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  2. Jung-Kai Chang: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  3. Yih-Ru Wu: Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  4. Tsung-Hsien Sun: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  5. Yang-Yu Cheng: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  6. Chien-Tai Ren: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  7. Mei-Hung Pan: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  8. Jin-Lin Wu: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  9. Kuo-Hsuan Chang: Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  10. Hwai-I Yang: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  11. Chiung-Mei Chen: Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan. cmchen@adm.cgmh.org.tw.
  12. Chung-Yi Wu: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan. cyiwu@icloud.com.
  13. Yun-Ru Chen: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan. yrchen@gate.sinica.edu.tw. ORCID
PMID: 36976478 DOI: 10.1007/s12035-023-03307-w

Abstract

Huntington's disease (HD) is a progressive and devastating neurodegenerative disease marked by inheritable CAG nucleotide expansion. For offspring of HD patients carrying abnormal CAG expansion, biomarkers that predict disease onset are crucially important but still lacking. Alteration of brain ganglioside patterns has been observed in the pathology of patients carrying HD. Here, by using a novel and sensitive ganglioside-focused glycan array, we examined the potential of anti-glycan auto-antibodies for HD. In this study, we collected plasma from 97 participants including 42 control (NC), 16 pre-manifest HD (pre-HD), and 39 HD cases and measured the anti-glycan auto-antibodies by a novel ganglioside-focused glycan array. The association between plasma anti-glycan auto-antibodies and disease progression was analyzed using univariate and multivariate logistic regression. The disease-predictive capacity of anti-glycan auto-antibodies was further investigated by receiver operating characteristic (ROC) analysis. We found that anti-glycan auto-antibodies were generally higher in the pre-HD group when compared to the NC and HD groups. Specifically, anti-GD1b auto-antibody demonstrated the potential for distinguishing between pre-HD and control groups. Moreover, in combination with age and the number of CAG repeat, the level of anti-GD1b antibody showed excellent predictability with an area under the ROC curve (AUC) of 0.95 to discriminate between pre-HD carriers and HD patients. With glycan array technology, this study demonstrated abnormal auto-antibody responses that showed temporal changes from pre-HD to HD.

Keywords

Auto-antibody GD1b Gangliosides Glycan array Huntington’s disease Pre-HD

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MeSH Term

Humans
Huntington Disease
Neurodegenerative Diseases
Brain
Biomarkers

Chemicals

Biomarkers
Journal Article

Word Cloud

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