engleski

Tau pathology in Down syndrome

Down syndrome (DS) patients are at high-risk to develop Alzheimer’s disease (AD) with an onset around 35 years of age, in part due to the presence of the triplication of chromosome 21 where the APP gene is located. Evaluation of autopsy cases revealed that at 35 years of age DS subjects display similar pathology to AD including amyloid plaques and tau containing neurofibrillary tangles (Hartley et al., 2015). A recent study of exosomes purified from blood revealed increased levels of tau and amyloid-β (Aβ) in DS children as young as 8 years of age (Hamlett et al., 2017). Moreover, abnormal tau phosphorylation has been observed in fetal tissue from DS (Milenkovic et al., 2017). Our aim was to evaluate tau and amyloid deposition in fetal as well as adult DS postmortem cases in comparison to sporadic AD and healthy controls using both 3HTHK5117 and 3H-PIB autoradiography, in comparison with AT8 tau and Amylo-Glo fluorescent staining, respectively. Autoradiography using 3H-THK5117 and 3H-PIB was performed on paraffin embedded hippocampal, temporal and frontal cortex sections from 3 fetal and 5 adult DS cases, 3 sporadic AD and 2 controls. Immunostaining using AT8 and Amylo-Glo staining was performed on adjacent sections. Both fetal and adult DS cases displayed 3H-THK5117 and 3H-PIB binding. 3H-THK5117 binding was higher in adult DS cases in comparison to sporadic AD cases. 3H-PIB binding was lower compared to 3HTHK5117 in all adult cases. AT8 and Amylo-Glo staining corresponded, respectively to 3H-THK5117 and 3H- PIB binding, both in adult DS and AD cases. In this study, we observed early and significant tau binding in DS cases. This study will allow new insights into tau pathology and could facilitate the understanding of neurofibrillary pathology in both DS cases as well as sporadic AD.

Down syndrome ; tau protein ; autoradiography ; tau-specific radiotracer THK5117 ; AT8 antibody ; 3H-PiB (Pittsburgh compound B) radioligand for fibrillar Abeta ; hippocampus ; neurofibrillary degeneration ; Alzheimer's disease

nije evidentirano