• Kaj Blennow, Daniela Diaz-Lucena, Henrik Zetterberg, Anna Villar-Pique, Andre Karch, Enric Vidal, Peter Hermann, Matthias Schmitz, Isidro Ferrer Abizanda, Inga Zerr, and Franc Llorens.
• Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
• J. Neurol. Neurosurg. Psychiatr. 2019 Aug 1; 90 (8): 846-853.

ObjectiveTo 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.MethodsCSF 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.ResultsCompared 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.ConclusionsNeurogranin 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.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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