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- W2034785078 abstract "Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and the most common cause of dementia. In addition to a need for novel disease-modifying treatments that would slow down or stop the progression of the pathology, there is also a demand for innovative diagnostic assays. Efforts are ongoing in imaging technologies (structural and functional) and in in vitro biomarkers, mostly focusing on cerebrospinal fluid. Less invasive assays using peripheral blood would obviously be preferred. Gene expression profiling from whole blood represents an attractive new avenue for biomarkers discovery. There are several lines of evidence why specific gene expression signatures could be identified from the blood of AD patients, such as alterations in immune responses including changes in lymphocyte and macrophage activation or releases of specific mediators. ExonHit's SpliceArray™ represents a novel generation of microarrays that incorporate a specific probe configuration, enabling an exhaustive monitoring of the transcriptome which includes splice variants. The Human Genome Wide SpliceArray which profile close to 21,000 human genes covering almost 140,000 splice events has been used in our biomarker discovery process. One hundred fifty AD and non AD patients have been screened using our platform; several algorithms were used to identify the best classification models for binary response. Support Vector Machine, a learning algorithm, provided a model that correctly assigned correctly more then 95% of the patients clinically probable AD and age/sex matched non AD patients using a 170 probe set signature. Functionally, this signature highlights genes involved in cholesterol and lipids homeostasis, APP processing, calcium signalling, cytoskeleton organisation, senile plaque formation, protein turnover and immune responses. This enhanced view of the human trancriptome led to the discovery of sensitive and specific AD related biomarkers from whole blood. A prototype diagnostic microarray will next be used in a prospective clinical trial enrolling cohorts of patients suffering from Alzheimer disease, non-AD dementia and neurodegenerative disease free patients." @default.
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- W2034785078 date "2008-07-01" @default.
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- W2034785078 title "P1-343: Discovery of blood gene expression biomarkers in Alzheimer's disease using the human genome-wide splice array" @default.
- W2034785078 doi "https://doi.org/10.1016/j.jalz.2008.05.924" @default.
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