Randall J. Bateman, M.D.
Charles F and Joanne Knight Distinguished Professor
The pathophysiology of Alzheimer disease and pharmacodynamic measurements of disease-modifying treatments. Our laboratory’s focus is on the causes, diagnosis and future treatments of Alzheimer disease. We directly measure the pathophysiology of Alzheimer disease in humans using multiple techniques and also perform in vitro cell culture experiments.
Our group uses a wide variety of assays and techniques from the most basic applications, such as quantitative measurement of stable-isotope labeled peptides to clinical translational studies in diagnostic and therapeutic biomarkers for Alzheimer’s disease. We have several ongoing studies including:
1) In Vivo metabolism of Aβ in Alzheimer`s Disease: We have pioneered a new technique to measure amyloid-beta metabolism in humans. Ongoing studies in Alzheimer’s disease and controls will address the hypothesis that there is a change in amyloid-beta metabolism in people who develop Alzheimer`s disease compared to people who do not.
2) Familial Adult Children Study: We are investigating the changes that occur in autosomal dominant Alzheimer disease; including structural changes by MRI, pathological changes by PET-PIB, functional changes by Clinical Dementia Rating and neuropsychometric testing, and pathophysiological changes in CSF biomarkers and CNS protein production and clearance rates.
3) Pharmacodynamic response of proposed disease modifying therapies for Alzheimer disease are tested by directly measuring the production, clearance and steady-state levels of the targeted proteins, including amyloid-beta. These studies quantitate targeted activity of therapeutics and provide evidence that these compounds are effective in humans.
4) CNS derived proteomics and measurements: We are currently investigating multiple other CNS derived proteins and are developing methods to measure hundreds of protein metabolism profiles in humans using highly sensitive nano-flow mass spectrometry and in vivo labeling techniques. Advanced bio-informatics, cutting edge mass spectrometry, and in vivo and in vitro labeling experiments are used for highly quantitative analysis of proteins.
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; the Dominantly Inherited Alzheimer Network (2012). New England Journal of Medicine
Huang Y, Potter R, Sigurdson W, Santacruz A, Shih S, Ju Y, Kasten T, Morris JC, Mintun M, Duntley S, Bateman RJ. Effects of Age and Amyloid Deposition on Aβ Dynamics in the Human Central Nervous System. Archives of Neurology. Published online September 12, 2011. doi:10.1001/archneurol.2011.235. NIHMS326112
Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ. Decreased Clearance of CNS Amyloid-β in Alzheimer’s Disease. Science December 2010: 330 (6012): 1774.
Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. Journal of Neuroscience 2010 30:6743-50.
Wildsmith KR, Han B, Bateman RJ. Method for the simultaneous quantitation of apolipoprotein E isoforms using tandem mass spectrometry. Analytical Biochemistry 2009 395:116-8.
Bateman RJ, Siemers ER, Mawuenyega KG, Wen G, Browning KR, Sigurdson WC, Yarasheski KE, Friedrich SW, Demattos RB, May PC, Paul SM, Holtzman DM. A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Annals of Neurology 2009.
Bateman RJ, Munsell LY, Morris JC, Swarm R, Yarasheski KE, Holtzman DM. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nature Medicine 2006 12:856-61.
Last Updated: 8/14/2012 5:11:05 PM