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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000200-02
Application #
8931483
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Varma, Vijay R; Oommen, Anup M; Varma, Sudhir et al. (2018) Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study. PLoS Med 15:e1002482
Seddighi, Sahba; Varma, Vijay R; An, Yang et al. (2018) SPARCL1 Accelerates Symptom Onset in Alzheimer's Disease and Influences Brain Structure and Function During Aging. J Alzheimers Dis 61:401-414
Shi, Liu; Baird, Alison L; Westwood, Sarah et al. (2018) A Decade of Blood Biomarkers for Alzheimer's Disease Research: An Evolving Field, Improving Study Designs, and the Challenge of Replication. J Alzheimers Dis 62:1181-1198
Wong, Dean F; Comley, Robert A; Kuwabara, Hiroto et al. (2018) Characterization of 3 Novel Tau Radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in Healthy Controls and in Alzheimer Subjects. J Nucl Med 59:1869-1876
Seddighi, Sahba; Varma, Vijay; Thambisetty, Madhav (2018) ?2-macroglobulin in Alzheimer's disease: new roles for an old chaperone. Biomark Med 12:311-314
An, Yang; Varma, Vijay R; Varma, Sudhir et al. (2018) Evidence for brain glucose dysregulation in Alzheimer's disease. Alzheimers Dement 14:318-329
Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872
Hohman, Timothy J; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA Neurol 75:989-998
Kueider, Alexandra M; An, Yang; Tanaka, Toshiko et al. (2017) Sex-Dependent Associations of Serum Uric Acid with Brain Function During Aging. J Alzheimers Dis 60:699-706
Toledo, Jon B; Arnold, Matthias; Kastenmüller, Gabi et al. (2017) Metabolic network failures in Alzheimer's disease: A biochemical road map. Alzheimers Dement 13:965-984

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