title: Comparison of the pathologic and pathogenic features in six different             regions of postmortem brains of three patients with fatal familial insomnia.
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.
authors.affiliation: School of Medicine, Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Wu-Ling
authors.initials: WL
authors.lastname: Xie
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Xia
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Zhang
authors.forename: Han-Shi
authors.initials: HS
authors.lastname: Gong
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Bian-Li
authors.initials: BL
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000328:Adult; D000818:Animals; D001344:Autopsy; D015153:Blotting, Western; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000473:pathology; D019286:Endopeptidase K / Q000235:genetics / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D034062:Insomnia, Fatal Familial / Q000235:genetics / Q000473:pathology*; D008297:Male; D008715:Methionine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013048:Specimen Handling; D013788:Thalamus / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D003062:Codon; D005904:Glial Fibrillary Acidic Protein; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D012333:RNA, Messenger; D014157:Transcription Factors; D008715:Methionine; D019286:Endopeptidase K; D010751:Phosphopyruvate Hydratase