Diagnostic and Prognostic Value of Plasma GFAP in Sporadic Creutzfeldt-Jakob Disease in the Clinical Setting of Rapidly Progressive Dementia.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Creutzfeldt-Jakob Syndrome*/blood ; Creutzfeldt-Jakob Syndrome*/diagnosis ; Creutzfeldt-Jakob Syndrome*/cerebrospinal fluid ; Glial Fibrillary Acidic Protein*/blood ; Glial Fibrillary Acidic Protein*/cerebrospinal fluid ; tau Proteins*/blood ; tau Proteins*/cerebrospinal fluid ; Biomarkers*/blood ; Biomarkers*/cerebrospinal fluid ; Dementia*/blood ; Dementia*/diagnosis ; Dementia*/cerebrospinal fluid ; Amyloid beta-Peptides*/blood ; Amyloid beta-Peptides*/cerebrospinal fluid; Humans ; Female ; Male ; Aged ; Middle Aged ; Prognosis ; Neurofilament Proteins/blood ; Neurofilament Proteins/cerebrospinal fluid ; Disease Progression ; 14-3-3 Proteins/cerebrospinal fluid ; 14-3-3 Proteins/blood

The diagnostic and prognostic value of plasma glial fibrillary acidic protein (pl-GFAP) in sporadic Creutzfeldt-Jakob disease (sCJD) has never been assessed in the clinical setting of rapidly progressive dementia (RPD). Using commercially available immunoassays, we assayed the plasma levels of GFAP, tau (pl-tau), and neurofilament light chain (pl-NfL) and the CSF total tau (t-tau), 14-3-3, NfL, phospho-tau181 (p-tau), and amyloid-beta isoforms 42 (Aβ 42 ) and 40 (Aβ 40 ) in sCJD ( n = 132) and non-prion RPD (np-RPD) ( n = 94) patients, and healthy controls (HC) ( n = 54). We also measured the CSF GFAP in 67 sCJD patients. Pl-GFAP was significantly elevated in the sCJD compared to the np-RPD and HC groups and affected by the sCJD subtype. Its diagnostic accuracy (area under the curve (AUC) 0.760) in discriminating sCJD from np-RPD was higher than the plasma and CSF NfL (AUCs of 0.596 and 0.663) but inferior to the 14-3-3, t-tau, and pl-tau (AUCs of 0.875, 0.918, and 0.805). Pl-GFAP showed no association with sCJD survival after adjusting for known prognostic factors. Additionally, pl-GFAP levels were associated with 14-3-3, pl-tau, and pl-NfL but not with CSF GFAP, Aβ 42 /Aβ 40 , and p-tau. The diagnostic and prognostic value of pl-GFAP is inferior to established neurodegeneration biomarkers. Nonetheless, pl-GFAP noninvasively detects neuroinflammation and neurodegeneration in sCJD, warranting potential applications in disease monitoring.

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Ricerca Corrente Ministero della Salute

Keywords: Alzheimer’s disease; Creutzfeldt–Jakob disease; GFAP; biomarker; co-pathology; neurodegeneration; neuroinflammation; prion

0 (Glial Fibrillary Acidic Protein)
0 (tau Proteins)
0 (Biomarkers)
0 (GFAP protein, human)
0 (Amyloid beta-Peptides)
0 (Neurofilament Proteins)
0 (neurofilament protein L)
0 (14-3-3 Proteins)

Creutzfeldt-Jakob Disease, Sporadic

Date Created: 20240525 Date Completed: 20240525 Latest Revision: 20240610

20240611

PMC11121136

10.3390/ijms25105106

38791145