ABSTRACT

Fatal Familial Insomnia (FFI) is one of the most popular genetic prion disease (gPrD) in China. Unlike the other types of human prion diseases, FFI patients show distinctive neuropathological characteristics, such as less deposition of PrP^Sc, low tissue infectivity and severe neuron losses in some special brain regions. Compared with other gPrDs, the positive reactions of cerebrospinal fluid (CSF) RT-QuIC of FFI patients were markedly low. However, the reactivities of RT-QuIC of the brain tissues, particularly different brain regions, of FFI cases are rarely described. In this study, three different brain regions from three FFI patients were subjected into two kinds of RT-QuIC assays using recombinant hamster PrP23-231 (rHaPrP23-231) and PrP90-231 (rHaPrP90-231) as the substrates, respectively. The results showed that the general RT-QuIC reactivities of the brains from FFI cases were significantly lower than that of sCJD. Analyses of the positive rates and the reactivities (lag time and rfu peak) of RT-QuIC identified that the homogenates of frontal lobe induced the most active reaction, followed by thalamus and callosum. The RT-QuIC reactivity in the tested brain sample was closely associated with the intensity of PK-resistant PrP^Sc. Moreover, we also verified that the sensitivity of the RT-QuIC of rHaPrP90-231 was much higher than that of rHaPrP23-231. Those data confirm that brain tissues of FFI patients are able to convert positive reactions in RT-QuIC and show regional-associated positive converting capacities.