Comprehensive mRNA expression profiling distinguishes tauopathies and identifies shared molecular pathways

• Published in: PloS one Vol. 4; no. 8; p. e6826
• Main Authors: Bronner, Iraad F, Bochdanovits, Zoltán, Rizzu, Patrizia, Kamphorst, Wouter, Ravid, Rivka, van Swieten, John C, Heutink, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.08.2009; Public Library of Science (PLoS)
• Subjects: Advertising executives; Aging; Alzheimer's disease; Apolipoprotein E; Apoptosis; Case-Control Studies; Cellular communication; Cluster Analysis; Dementia disorders; Disorders; DNA binding proteins; DNA microarrays; DNA Primers; DNA probes; FOXO3 protein; Frontotemporal dementia; Gene expression; Gene Expression Profiling; Genes; Genetic research; Genetics and Genomics/Comparative Genomics; Genetics and Genomics/Gene Expression; Genome-Wide Association Study; Genomes; Genomics; Humans; Insulin-like growth factors; Kinases; Messenger RNA; Nervous system diseases; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - physiopathology; Neurological diseases; Neurological Disorders/Alzheimer Disease; Neurological Disorders/Movement Disorders; Neurological Disorders/Neurogenetics; Niemann-Pick disease; Oligonucleotide Array Sequence Analysis; Paralysis; Pathology; Pathways; Patients; Polymerase Chain Reaction; Probes; Progressive supranuclear palsy; RNA, Messenger - genetics; Rodents; Tau protein; tau Proteins - genetics; tau Proteins - physiology; Temporal lobe; Transcription (Genetics); Transcription factors; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0006826

Understanding the aetiologies of neurodegenerative diseases such as Alzheimer's disease (AD), Pick's disease (PiD), Progressive Supranuclear Palsy (PSP) and Frontotemporal dementia (FTD) is often hampered by the considerable clinical and molecular overlap between these diseases and normal ageing. The development of high throughput genomic technologies such as microarrays provide a new molecular tool to gain insight in the complexity and relationships between diseases, as they provide data on the simultaneous activity of multiple genes, gene networks and cellular pathways. We have constructed genome wide expression profiles from snap frozen post-mortem tissue from the medial temporal lobe of patients with four neurodegenerative disorders (5 AD, 5 PSP, 5 PiD and 5 FTD patients) and 5 control subjects. All patients were matched for age, gender, ApoE-epsilon and MAPT (tau) haplotype. From all groups a total of 790 probes were shown to be differently expressed when compared to control individuals. The results from these experiments were then used to investigate the correlations between clinical, pathological and molecular findings. From the 790 identified probes we extracted a gene set of 166 probes whose expression could discriminate between these disorders and normal ageing. From genome wide expression profiles we extracted a gene set of 166 probes whose expression could discriminate between neurological disorders and normal ageing. This gene set can be further developed into an accurate microarray-based classification test. Furthermore, from this dataset we extracted a disease specific set of genes and identified two aging related transcription factors (FOXO1A and FOXO3A) as possible drug targets related to neurodegenerative disease.