IC‐P‐098: PHOSPHORYLATION OF SPECIFIC TAU SITES IS ASSOCIATED WITH LOSS OF WHITE MATTER INTEGRITY IN AUTOSOMAL DOMINANT ALZHEIMER DISEASE

• DOI: 10.1016/j.jalz.2019.06.4941
• Publication Date: 2019-10-18T12:00:42Z
• Authors: Jeremy F. Strain; Julie Wisch; Collin B. Kilgore; Eric McDade; Yan Li; Nicolas R. Barthé...; Brian A. Gordon; Jason Hassenstab; Anne M. Fagan; John C. Morris; Tammie L.S. Benzi...; Randall Bateman; Beau M. Ances
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer disease(AD). Tau can be phosphorylated at multiple positions vary over AD disease stage may quantify severity pathology or neurodegeration. We evaluated whether phosphorylation three sites (pt217, pt181, pt205) total associated with white matter track (WMT) integrity within autosomal dominant AD(ADAD). ADAD are a younger cohort exhibit fewer age-related comorbidities making this an ideal examine changes. Cerebrospinal fluid (CSF) diffusion tensor imaging was obtained from 71 mutation positive 40 negative participants the Dominantly Inherited Network (DIAN). CSF p-tau/tau ratio on each site by nanoAcquity UPLC system coupled Fusion Tribrid mass spectrometer. Diffusivity maps were calculated evaluate WMT integrity. A voxel-wise correlation using permutation testing assessed relationship between diffusivity age included as covariate. created averaging skeletal voxels overlaid regions interest. Linear models constructed for predicting individually amalgamated into single composite derived principal component analysis. Variables incorporated model include age, amyloid, hyperintensities, precuneus volume, site. Fractional anisotropy (FA) radial (DR) callosal fibers correlated pt205 but not pt217, carriers(p<0.05 corrected). The primary explained 70% variance top contributors including cingulum, forceps major(FM), corpus callosum. regression revealed only predicted PCA composite(p=0.005). In significantly FA DR FM(FA p=0.01; p=0.037) PCC(FA p=0.0023; p=0.003).