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Senior Investigator

Madhav Thambisetty, M.D., Ph.D.

Unit of Clinical & Translational Neuroscience

Brain Aging and Behavior Section
Building 251 Room 04B317
Bayview Blvd
Baltimore 21224
Office: 410-558-8572
Lab: 410-558-8572

Madhav Thambisetty is a Board-certified neurologist with sub-specialty training in cognitive/behavioral neurology and sleep disorders. He completed both residency and fellowship training in the Department of Neurology at Emory University School of Medicine in Atlanta. Prior to training in Neurology, he was awarded a PhD (DPhil) in Clinical Pharmacology from the University of Oxford where he pursued doctoral studies on a Felix scholarship. His PhD thesis examined the role of synaptic remodeling in the actions of anti-depressant treatments. In 2004, he was awarded a research fellowship by the Alzheimer’s Society of the United Kingdom to pursue research into ‘Blood biomarkers of Alzheimer’s Disease’ at the Institute of Psychiatry, King’s College, London. He was elected to the Emanoel Lee medical research fellowship at St. Cross College, Oxford in 2004. In 2016, he was awarded the Norman Geschwind prize in Behavioral Neurology by the American Academy of Neurology (AAN). He is currently also an Adjunct Associate Professor of Neurology at the Johns Hopkins University School of Medicine.

Although rapid strides have been made in our understanding of the basic biology of Alzheimer's disease (AD), there is concern that this knowledge has not been translated into earlier diagnosis and/or effective treatments for patients. The overall goals of the Clinical and Translational Neuroscience Unit in the Laboratory of Behavioral Neuroscience are to enhance understanding of disease mechanisms operating in AD as well as to identify novel biomarkers that might be predictive of disease before the onset of clinical symptoms. To achieve these goals, we use several approaches including:

1. Applying mass spectrometry-based proteomics and metabolomics for the discovery of novel biomarkers   predictive of disease before symptom onset.
2. Relating genetic and environmental risk factors to changes in brain structure, function and pathology during aging.

While these studies rely primarily on clinical and neuroimaging datasets available within the Baltimore Longitudinal Study of Aging (BLSA), other datasets, such as those available through the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) are also used in these analyses.

In our biomarker discovery studies, we use archived blood samples collected through the BLSA to identify changes over time in the concentrations of proteins and small metabolites that may be predictive of early cognitive decline and neuropathological changes associated with AD.

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  • 1) Varma VR, Varma S, An Y, Hohman TJ, Seddighi S, Casanova R, Beri A, Dammer EB, Seyfried NT, Pletnikova O, Moghekar A, Wilson MR, Lah JJ, O'Brien RJ, Levey AI, Troncoso JC, Albert MS, Thambisetty M (2017)
  • Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway
  • Mol Psychiatry, 2017 Jan;22(1), 13-23
  • 2) Snowden SG, Ebshiana AA, Hye A, An Y, Pletnikova O, O'Brien R, Troncoso J, Legido-Quigley C, Thambisetty M (2017)
  • Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study
  • PLoS Med. 2017 Mar 21;14(3):e1002266
  • 3) Thambisetty M (2017)
  • Understanding mechanisms and seeking cures for Alzheimer's disease: Why we must be "extraordinarily diverse"
  • 4) Seddighi S, Varma VR, An Y, Varma S, Beason-Held LL, Tanaka T, Kitner-Triolo MH, Kraut MA, Davatzikos C, Thambisetty M (2017)
  • SPARCL1 Accelerates Symptom Onset in Alzheimer’s Disease and Influences Brain Structure and Function During Aging
  • 5) An Y, Varma VR, Varma S, Casanova R, Dammer E, Pletnikova O, Chia CW, Egan JM, Ferrucci L, Troncoso J, Levey AI, Lah J, Seyfried NT, Legido-Quigley C, O’ Brien R, Thambisetty M (2017)
  • Evidence for Brain Glucose Dysregulation in Alzheimer’s Disease
  • 6) Vijay R. Varma, Anup M. Oommen, Sudhir Varma, Ramon Casanova, Yang An, Ryan M. Andrews, Richard O’Brien, Olga Pletnikova, Juan C. Troncoso, Jon Toledo, Rebecca Baillie, Matthias Arnold, Gabi Kastenmueller, Kwangsik Nho, Murali Doraiswamy, Andrew J. Saykin, Rima Kaddurah-Daouk, Cristina Legido-Quigley, Madhav Thambisetty (2017)
  • Brain and Blood Metabolite Signatures of Pathology and Progression in Alzheimer’s Disease
  • PLOS MEDICINE (in press) PMCID:pending
  • 7) Chuang YF, An Y, Bilgel M, Wong DF, Troncoso JC, O'Brien RJ, Breitner JC, Ferruci L, Resnick SM, Thambisetty M (2016)
  • Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation
  • Mol Psychiatry, Jul;21(7), 910-5
  • 8) Blood metabolite markers of cognitive performance and brain function in aging (2016)
  • Simpson BN, Kim M, Chuang YF, Beason-Held L, Kitner-Triolo M, Kraut M, Lirette ST, Windham BG, Griswold ME, Legido-Quigley C, Thambisetty M
  • J Cereb Blood Flow Metab, Jul;36(7), 1212-23
  • 9) Casanova R, Varma S, Simpson B, Kim M, An Y, Saldana S, Riveros C, Moscato P, Griswold M, Sonntag D, Wahrheit J, Klavins K, Jonsson PV, Eiriksdottir G, Aspelund T, Launer LJ, Gudnason V, Legido Quigley C, Thambisetty M (2016)
  • Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals
  • Alzheimers Dement, Jul;12(7), 815-22
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