Korpela Sara, Sundblom Jimmy, Zetterberg Henrik, Constantinescu Radu, Svenningsson Per, Paucar Martin, Niemelä Valter
Department of Medicine, Neurology, Västerås Central Hospital, Västerås, Sweden.
Department of Medical Sciences, Neurosurgery, Uppsala University, Uppsala, Sweden.
J Neurol Sci. 2024 Apr 15;459:122979. doi: 10.1016/j.jns.2024.122979. Epub 2024 Mar 30.
Huntington's disease (HD) is a hereditary neurodegenerative disease, currently lacking disease-modifying treatments. Biomarkers are needed for objective assessment of disease progression. Evidence supports both complex protein aggregation and astrocyte activation in HD. This study assesses the 42 amino acid long amyloid beta (Aβ42) and glial fibrillary acidic protein (GFAP) as potential biomarkers in the cerebrospinal fluid (CSF) of HD mutation carriers.
CSF from participants was obtained from three sites in Sweden. Clinical symptoms were graded with the composite Unified Huntington's disease rating scale (cUHDRS). Protein concentrations were measured using ELISA. Pearson correlations were calculated to assess disease progression association. Results were adjusted for age and collection site.
The study enrolled 28 manifest HD patients (ManHD), 13 premanifest HD gene-expansion carriers (PreHD) and 20 controls. Aβ42 levels did not differ between groups and there was no correlation with measures of disease progression. GFAP concentration was higher in ManHD (424 ng/l, SD 253) compared with both PreHD (266 ng/l, SD 92.4) and controls (208 ng/l, SD 83.7). GFAP correlated with both cUHDRS (r = -0.77, p < 0.001), and 5-year risk of disease onset (r = 0.70, p = 0.008).
We provide evidence that indicates CSF Aβ42 has limited potential as a biomarker for HD. GFAP is a potential biomarker of progression in HD. Validation in larger cohorts measuring GFAP in blood and CSF would be of interest.
亨廷顿舞蹈症（HD）是一种遗传性神经退行性疾病，目前缺乏改善病情的治疗方法。需要生物标志物来客观评估疾病进展。有证据支持HD中存在复杂的蛋白质聚集和星形胶质细胞活化。本研究评估了42个氨基酸长的淀粉样β蛋白（Aβ42）和胶质纤维酸性蛋白（GFAP）作为HD突变携带者脑脊液（CSF）中的潜在生物标志物。
参与者的脑脊液取自瑞典的三个地点。临床症状用综合统一亨廷顿舞蹈症评定量表（cUHDRS）进行分级。使用酶联免疫吸附测定法（ELISA）测量蛋白质浓度。计算Pearson相关性以评估疾病进展关联。结果针对年龄和采集地点进行了调整。
该研究纳入了28名显性HD患者（ManHD）、13名症状前HD基因扩展携带者（PreHD）和20名对照。各组之间Aβ42水平无差异，且与疾病进展指标无相关性。与PreHD（266 ng/l，标准差92.4）和对照（208 ng/l，标准差83.7）相比，ManHD中GFAP浓度更高（424 ng/l，标准差253）。GFAP与cUHDRS（r = -0.77，p < 0.001）以及5年疾病发病风险（r = 0.70，p = 0.008）均相关。
我们提供的证据表明脑脊液Aβ42作为HD生物标志物的潜力有限。GFAP是HD进展的潜在生物标志物。在更大队列中对血液和脑脊液中的GFAP进行测量的验证将很有意义。
