Myelin Basic Protein Is Associated with White Matter Integrity in 4-Repeat Tauopathies (P5.178)

OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) myelin basic protein (MBP) is associated with neuroimaging evidence of white matter (WM) integrity in the 4-repeat tauopathies (4Rtau), including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). BACKGROUND: Genome wide association studies identified single nucleotide polymorphisms in the myelin oligodendrocyte basic protein (MOBP) gene as risk factors for PSP and CBD. Prior work also demonstrated that a risk allele in the MOBP gene is associated with reduced WM integrity and reduced survival in frontotemporal lobar degeneration (FTLD). However, biochemical analysis of an associated myelin protein, MBP, in 4Rtau has not been evaluated. In this study, we evaluate whether CSF MBP is associated with diffusion tensor imaging (DTI) metrics of WM integrity. DESIGN/METHODS: CSF MBP and DTI were obtained from 14 probable 4Rtau patients (8 clinically diagnosed PSP and 6 corticobasal syndrome). DTI volumes were processed using ANTs software, and we computed DTI metrics of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) to measure WM integrity. Regression analyses related CSF to DTI metrics. RESULTS: Higher levels of CSF MBP were related to lower FA in the inferior fronto-occipital fasciculus, parieto-occipital corpus callosum (CC), anterior thalamic radiation, angular gyrus, superior longitudinal fasciculus (SLF), cerebellum, superior parietal lobule, supramarginal gyrus, and frontal CC. We also observed that MBP CSF was associated with lower RD in the cerebral peduncle and SLF, and with lower AD in the parieto-occipital CC, inferior fronto-occipital fasciculus, and central CC. CONCLUSION: CSF measurement of MBP is associated with WM integrity in regions previously associated with 4Rtau pathology, including the cerebral peduncle and SLF. Further work is required to identify the role of CSF MBP as a prognostic/diagnostic biomarker for 4Rtau. STUDY SUPPORT: NIH (AG0435043, AG017586, NS044266, NS088341), Dana Foundation, and Wyncote Foundation Disclosure: Dr. Firn has nothing to disclose. Dr. Irwin has nothing to disclose. Dr. Grossman has received personal compensation for activities with GE Whitney Symposium as an invited speaker. Dr. Grossman has received personal compensation in an editorial capacity for Neurology. Dr. McMillan has nothing to disclose.