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Principal Investigator  
Principal Investigator's Name: Jose Bras
Institution: UCL, Institute of Neurology
Department: Molecular Neuroscience
Country:
Proposed Analysis: We have recently generated data showing that CSF Neurogranin levels are specifically elevated in Alzheimer’s disease (AD) (in press). We have previously used ADNI samples to show a similar effect (Portelius E. 2015). Both results suggest that CSF Neurogranin might be a useful biomarker for AD. In addition, we have also recently shown that, in the ADNI cohort, CSF neurofilament light concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time (Zetterberg H, 2015). Recently it was shown that a haplotype in the Neurogranin gene was associated with expression levels (Ohi K. 2013), but, to the best of our knowledge, an association with actual Neurogranin levels has not been performed. The current proposal aims to integrate these findings with the genetic data from the ADNI dataset. The main goals are to identify genetic variants that influence levels of CSF Neurogranin and neurofilament light. We will use previously generated levels of CSF Neurogranin and neurofilament light as quantitative traits in AD and progressive MCI groups and test for association with genetic data from WGS in the ADNI cohort. We will also compare results with the previously reported haplotype involved in regulating Neurogranin expression.
Additional Investigators  
Investigator's Name: Henrik Zetterberg
Proposed Analysis: We have recently generated data showing that CSF Neurogranin levels are specifically elevated in Alzheimer’s disease (AD) (in press). We have previously used ADNI samples to show a similar effect (Portelius E. 2015). Both results suggest that CSF Neurogranin might be a useful biomarker for AD. In addition, we have also recently shown that, in the ADNI cohort, CSF neurofilament light concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time (Zetterberg H, 2015). Recently it was shown that a haplotype in the Neurogranin gene was associated with expression levels (Ohi K. 2013), but, to the best of our knowledge, an association with actual Neurogranin levels has not been performed. The current proposal aims to integrate these findings with the genetic data from the ADNI dataset. The main goals are to identify genetic variants that influence levels of CSF Neurogranin and neurofilament light. We will use previously generated levels of CSF Neurogranin and neurofilament light as quantitative traits in AD and progressive MCI groups and test for association with genetic data from WGS in the ADNI cohort. We will also compare results with the previously reported haplotype involved in regulating Neurogranin expression.