High Proportions of GAP43 Positivity in the Cerebrospinal Fluids of Patients with Sporadic and Certain Types of Genetic Creutzfeldt-Jakob Diseases by Western Blot Analysis

Growth-associated protein-43 (GAP43) is a neuronal protein essential for synaptic function and plasticity, and its reduction has been observed in brains of prion diseases (PrDs) and rodent models. However, its status in the cerebrospinal fluid (CSF) of patients with PrDs remains unclear. CSF samples from 140 PrD cases, including 48 sCJD, 35 T188K-gCJD, 22 E200K-gCJD, 35 D178N-FFI, and 36 non-PrD controls, were analyzed for GAP43 by Western blot. The results were compared with 14-3-3 and calmodulin (CaM) detected by WB, and associated with clinical features. GAP43 positivity was significantly higher in sCJD (70.83%), T188K-gCJD (65.71%), and E200K-gCJD (72.73%) than in non-PrD controls (27.78%). The sensitivity and specificity of GAP43 (around 70-75%) were comparable to 14-3-3 and CaM, though inferior to RT-QuIC and total tau reported elsewhere. CSF GAP43 positivity correlated with sCJD-associated MRI changes, periodic sharp-wave complexes (PSWC) on EEG, and with 14-3-3 and CaM positivity. Our data here indicate the feasibility of usage of GAP43 by Western blot analysis as a diagnostic, at least as a screening, biomarker for sCJD and certain types of gPrDs.