D011 Skin Tau quantification as a novel biomarker in Huntington's disease

<h3>Background</h3> Recent studies have shown abnormal tau accumulation in the brains of Huntington9s disease (HD) patients, highlighting tau protein dysregulation as a key aspect of its pathogenesis. Particularly, the role of 4R tau isoforms has been connected to HD progression and cognitive decline. Although tau protein levels have been examined in cerebrospinal fluid (CSF) and plasma of HD mutation carriers, novel research in primary tauopathies suggests that skin tau detection could be a promising biomarker. <h3>Aims</h3> This study investigates skin tau quantification in HD as a potential biomarker for disease severity and mutation carrier stratification. <h3>Methods</h3> Skin biopsies from 23 HD patients and 8 healthy controls were collected from the ankle region (Figure1) and analyzed using ELISA to quantify tau levels, normalizing to total skin protein. Disease severity was assessed with clinical and neuropsychological scales, and gray matter volume (GMV) was evaluated from T1-weighted images via voxel-based morphometry. <h3>Results</h3> Skin tau levels differed significantly (χ² = 8.03, p = 0.02), with higher concentrations in manifest HD carriers (HDISS 2-3) compared to controls and premanifest individuals (HDISS 0-1). A significant correlation was found between skin tau levels and CAG repeat length, CAG-Age-Product score, UHDRS TMS, cUHDRS, and neuropsychological scales. Group analysis showed a significant association between GMV in the caudate nucleus and putamen and skin tau levels, independent of age and gender (Figure 2). <h3>Conclusions</h3> Skin tau quantification may be a novel, valuable biomarker for Huntington9s disease, correlating with disease severity and potentially enhancing stratification of HD mutation carriers.