D02 Cerebrospinal fluid amyloid beta and glial fibrillary acidic protein concentrations in huntington’s disease

Abstract

<h3>Background</h3> Huntington’s disease (HD) is a monogenic disease lacking a cure. Biomarkers are needed for objective assessment of disease progression. Evidence supports both complex protein aggregation and astrocyte activation in HD. <h3>Aims</h3> This study assesses the potential of the 42 amino acid long amyloid beta (Aβ42) and glial fibrillary acidic protein (GFAP) as biomarkers in cerebrospinal fluid (CSF) of HD mutation carriers. <h3>Methods</h3> CSF was obtained from manifest HD patients (ManHD), premanifest HD-gene-expansion carriers (PreHD) and gene-negative controls (controls). Disease Burden Score (DBS) and Total Functional Capacity (TFC) were calculated. Protein concentrations were measured by enzyme-linked immunosorbent assays (ELISA) and intergroup differences were analyzed using Mann-Whitney U test. Association with disease stage was assessed with Spearman correlations and age-adjustment was included in the statistical tests. <h3>Results</h3> The study enrolled 27 ManHD and 13 PreHD subjects. The number of controls differed in the analysis of Aβ42 and GFAP (n = 19, and 8 respectively). Aβ42 levels were higher in ManHD (mean 741 ng/l, SD 361) compared with PreHD (mean 468 ng/l, SD 184) (p = 0.025). The GFAP concentration was higher in ManHD (mean 435 ng/l, SD 255) compared with both PreHD (mean 266 ng/l, SD 92.4) (p = 0.040) and controls (mean 208 ng/l, SD 83.7) (p = 0.011). GFAP correlated with DBS (r = 0.361, p = 0.028), TFC (r = −0.463, p = 0.005), and with 5-year risk of onset in PreHD (r = 0.694, p = 0.008). There was no correlation between Aβ42 concentration and DBS, TFC or 5-year risk of onset. <h3>Conclusion</h3> CSF Aβ42 levels did not correlate with disease stage suggesting no Aβ aggregation in HD. GFAP is a potential biomarker in HD with association to disease stage. Validation in a larger HD cohort is needed.