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The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.
Gogishvili, Dea; Honey, Madison I J; Verberk, Inge M W; Vermunt, Lisa; Hol, Elly M; Teunissen, Charlotte E; Abeln, Sanne.
Afiliação
  • Gogishvili D; Bioinformatics, Computer Science Department, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Honey MIJ; AI Technology for Life, Department of Computing and Information Sciences, Department of Biology, Utrecht University, Utrecht, The Netherlands.
  • Verberk IMW; Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.
  • Vermunt L; Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.
  • Hol EM; Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.
  • Teunissen CE; Department of Translational Neuroscience, UMC Utrecht Brain Centre, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
  • Abeln S; Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.
J Neurochem ; 2024 Sep 17.
Article em En | MEDLINE | ID: mdl-39289040
ABSTRACT
Glial fibrillary acidic protein (GFAP) is a well-established biomarker of reactive astrogliosis in the central nervous system because of its elevated levels following brain injury and various neurological disorders. The advent of ultra-sensitive methods for measuring low-abundant proteins has significantly enhanced our understanding of GFAP levels in the serum or plasma of patients with diverse neurological diseases. Clinical studies have demonstrated that GFAP holds promise both as a diagnostic and prognostic biomarker, including but not limited to individuals with Alzheimer's disease. GFAP exhibits diverse forms and structures, herein referred to as its proteoform complexity, encompassing conformational dynamics, isoforms and post-translational modifications (PTMs). In this review, we explore how the proteoform complexity of GFAP influences its detection, which may affect the differential diagnostic performance of GFAP in different biological fluids and can provide valuable insights into underlying biological processes. Additionally, proteoforms are often disease-specific, and our review provides suggestions and highlights areas to focus on for the development of new assays for measuring GFAP, including isoforms, PTMs, discharge mechanisms, breakdown products, higher-order species and interacting partners. By addressing the knowledge gaps highlighted in this review, we aim to support the clinical translation and interpretation of GFAP in both CSF and blood and the development of reliable, reproducible and specific prognostic and diagnostic tests. To enhance disease pathology comprehension and optimise GFAP as a biomarker, a thorough understanding of detected proteoforms in biofluids is essential.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: J Neurochem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: J Neurochem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda