期刊
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
卷 90, 期 8, 页码 846-853出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jnnp-2018-320155
关键词
neurogranin; alzheimer's disease; tau; neurofilament light; neurodegenerative dementias; creutzfeldt-jakob disease; cerebrospinal fluid
资金
- Spanish Ministry of Health-Instituto Carlos III (Miguel Servet programme) [CP16/00041]
- Robert Koch Institute through the Federal Ministry of Health [1369-341]
- Torsten Soderberg Foundation
- Swedish Research Council
- Swedish Alzheimer Foundation
- Swedish Brain Foundation
- ALF/LUA Vastra Gotalandsregionen
- European Research Council
- Knut and Alice Wallenberg Foundation
- UK Dementia Research Institute
- Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V-A Espana-Francia-Andorra (POCTEFA) (POCTEFA 2014-2020) programme
Objective To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer's disease (AD), and associated with neuronal degeneration in brain tissue. Methods CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied. Results Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p<0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p<0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p<0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p<0.001. In CJD, neurogranin positively correlated with tau (r=0.55, p<0.001) and was higher in 14-3-3-positivity (p<0.05), but showed no association with NFL (r=0.08, p=0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers. Conclusions Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner.
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