comprehensive mrna expression profiling distinguishes tauopathies and identifies shared molecular pathways综合mrna表达分析区分tauopathies并识别共同的分子途径.pdfVIP

Comprehensive mRNA Expression Profiling Distinguishes Tauopathies and Identifies Shared Molecular Pathways 1 ´ 1 1 3 4 Iraad F. Bronner , Zoltan Bochdanovits , Patrizia Rizzu , Wouter Kamphorst , Rivka Ravid , John C. van 2 1 Swieten , Peter Heutink * 1 Section Medical Genomics, Department of Clinical Genetics, VU University Medical Center, and Center for Neurogenomics and Cognitive Research, VU University Medical Center and VU University, Amsterdam, the Netherlands, 2 Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands, 3 Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands, 4 Netherlands Brain Bank, Amsterdam, the Netherlands Abstract Background: 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. Methodology/Principal Findings: 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-e and MAPT (tau) haplotype. From all groups a total of 790 probes were shown to be differently expressed when compared to