Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia

Xie,Wu-Ling; Shi,Qi; Xia,Sheng-Li; Zhang,Bao-Yun; Gong,Han-Shi; Wang,Shao-Bin; Xu,Yin; Guo,Yan; Tian,Chan; Zhang,Jin; Xu,Bian-Li; Liu,Yong; Dong,Xiao-Ping

doi:10.3892/ijmm.2012.1194

Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia

Authors:
- Wu-Ling Xie
- Qi Shi
- Sheng-Li Xia
- Bao-Yun Zhang
- Han-Shi Gong
- Shao-Bin Wang
- Yin Xu
- Yan Guo
- Chan Tian
- Jin Zhang
- Bian-Li Xu
- Yong Liu
- Xiao-Ping Dong
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Affiliations: School of Medicine, Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, P.R. China, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China, Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan 450016, P.R. China, School of Medicine, Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: November 22, 2012 https://doi.org/10.3892/ijmm.2012.1194
Pages: 81-90

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Abstract

Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by rapidly progressive insomnia, prominent autonomic alterations and behavioral disturbance. The D178N mutation of the prion protein gene (PRNP) on chromosome 20 in conjunction with methionine at codon 129 is a molecular feature. Although the neuropathological characteristics of FFI are well documented, the neuropathologic and pathogenic features of FFI patients remain poorly understood. Six brain regions of postmortem brains from 3 FFI patients were examined using immunohistochemistry, western blot analyses and quantitative real-time PCR. In all 3 brain specimens, reactive astrogliosis was found to be more severe in the thalamus than in the cortex regions. Western blot analyses showed that all three brains expressed PrP, but only 2 were associated with significantly weak proteinase K (PK) resistance. However, the conformational stabilities of PrPSc in the 3 FFI brains were significantly weaker than those presented in a G114V genetic Creutzfeldt-Jakob disease (gCJD) case. Immunohistochemistry and western blot analyses showed comparable amounts of neuron-specific enolase (NSE)-positive stained cells and NSE protein among the different regions in the three brains. In addition, the transcriptional levels of glial fibrillary acidic protein (GFAP) and NSE-specific mRNAs were coincident with the expression of these proteins. In conclusion, in the present study, we described the detailed regional neuropathology of FFI cases.

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