TY  - JOUR
AU  - Maass, Fabian
AU  - Thomas, Carolina
AU  - Kurvits, Lille
AU  - Hermann, Peter
AU  - Schmitz, Matthias
AU  - Bähr, Mathias
AU  - Stadelmann, Christine
AU  - Zechel, Sabrina
AU  - Canaslan, Sezgi
AU  - Zerr, Inga
TI  - Alterations in cerebrospinal fluid levels of myelin- and oligodendrocyte-related proteins in sporadic Creutzfeldt–Jakob disease
JO  - Acta Neuropathologica Communications
VL  - 14
IS  - 1
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DZNE-2026-00239
SP  - 51
PY  - 2026
AB  - Recent evidence suggests glial dysfunction, particularly involving oligodendrocytes and myelin, as an important part of the primary disease mechanism of sporadic Creutzfeldt–Jakob disease. To the best of our knowledge, cerebrospinal fluid (CSF) biomarkers reflecting oligodendrocyte or myelin damage have not yet been systematically investigated in this context. CSF samples from patients with sporadic Creutzfeldt–Jakob disease (CJD), Alzheimer's disease (AD) and non-neurodegenerative controls (n = 18, respectively) were included in the study, and levels of myelin basic protein (MBP), neural/glial antigen 2 (NG2) and cyclic nucleotide 3′-phosphodiesterase (CNPase) were quantified. Additionally, p25-positive cells were quantified in autopsy tissue from the frontal and parietal cortical regions of five patients with CJD and four controls. In the primary cohort, MBP quantification revealed significantly higher CSF levels in CJD compared to AD (p = 0.004) and controls (p = 0.0001) and this difference remained significant after adjustment for age and neurofilament light chain (NfL), indicating that MBP elevations cannot be explained solely by neuroaxonal degeneration. Significant differences were also found for CNPase in CJD compared to AD (p = 0.0011) and controls (p = 0.0004). There were no differences in NG2 levels (p > 0.05) among the groups. However, no significant differences were observed in the total number of p25-positive mature oligodendrocytes between CJD and controls in cortical brain tissue (p > 0.05). Additionally, MBP and NfL were quantified in a second cohort of 28 CJD and 20 biomarker-defined AD patients. In this cohort, characterized by more advanced AD pathology, MBP strongly covaried with NfL and no longer differed between diagnostic groups, suggesting a greater influence of neuroaxonal injury on MBP levels in advanced disease stages. In conclusion, in CJD, MBP elevations appear to be only partly related to neuroaxonal degeneration and may reflect disease-related myelin involvement.The online version contains supplementary material available at 10.1186/s40478-026-02247-5.
KW  - Biomarker (Other)
KW  - CNPase (Other)
KW  - Cerebrospinal fluid (Other)
KW  - Creutzfeldt–Jakob disease (Other)
KW  - Myelin basic protein (Other)
KW  - NG2 (Other)
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1186/s40478-026-02247-5
UR  - https://pub.dzne.de/record/285457
ER  -