Understanding mechanisms and seeking novel biomarkers in Alzheimer's disease

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Over the reporting period for the last year, we have published on the relationships between genetic risk for obesity associated with a common variant in the FTO gene and several intermediate phenotypes such as impulsivity, dietary patterns and brain function during aging. Understanding the pleiotropic effects of genetic risk underlying obesity is critical if we are to develop behavioral interventions targeting life-style related risk factors such as obesity. We have examined the relationships between midlife obesity and the age-at-onset of AD as well as its relationship with AD pathology. In our biomarker studies, we have reported on the depeletion of three phosphatidylcholine molecules in the plasma of patients with Alzheimer's disease (AD). We have subsequently extended these findings to test their association with trajectories of cognitive decline in non-demented older individuals. A multi-platform metabolomics approach using mass spectrometry and nuclear magnetic resonance has been applied to discover cerebrospinal fulid biomarkers in AD.