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Cerebral gene expression profiles in sporadic Creutzfeldt–Jakob disease
Author(s) -
Xiang Wei,
Windl Otto,
Westner Ingo M.,
Neumann Manuela,
Zerr Inga,
Lederer Rosa M.,
Kretzschmar Hans A.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20551
Subject(s) - downregulation and upregulation , biology , microarray , gene , microarray analysis techniques , gene expression , gene expression profiling , dna microarray , microbiology and biotechnology , genetics
Abstract The pathomechanism of sporadic Creutzfeldt–Jakob disease (sCJD) in the central nervous system is insufficiently understood. The aims of this study were to identify differentially regulated genes in the frontal cortex of sCJD and to profile the gene expression patterns in sCJD by using Affymetrix HGU133A microarrays (Affymetrix, Santa Clara, CA). The microarray data were generated by dChip and analyzed by Significance Analysis of Microarray (SAM) software. A comparison between control and sCJD samples identified 79 upregulated and 275 downregulated genes, which showed at least 1.5‐ and 2‐fold changes, respectively, in sCJD frontal cortex, with an estimated false discovery rate of 5% or less. The major alterations in sCJD brains included upregulation of the genes encoding immune and stress‐response factors and elements involved in cell death and cell cycle, as well as prominent downregulation of genes encoding synaptic proteins. A comparison of the molecular subtypes of sCJD showed various expression patterns associated with particular subtypes. The range of the upregulated genes and the degree of the increased expression appeared to be correlated with the degree of the neuropathological alterations in particular subtypes. Conspicuously, sCJD brains showed a great similarity with ageing human brains, both in the global expression patterns and in the identified differentially expressed genes. Ann Neurol 2005;58:242–257