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Randall Bateman, MD

Randall Bateman is the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine. Dr. Bateman’s central goal is to understand the pathophysiology of Alzheimer’s disease to better develop treatments and diagnostic biomarkers. To this end, he has pioneered the central nervous system Stable Isotope Labeling Kinetics (SILK) measurements in humans. Through his lab based research, Dr. Bateman led the development of the stable isotope-linked kinetics, an in vivo method of measuring protein kinetics in humans to better understand the pathophysiology of Alzheimer’s disease and develop better tests and treatments. This approach has provided key insights and information about trial design. Specifically, this novel method has been used to test and accelerate development of multiple drugs for Alzheimer’s. His lab now has preliminary data that plasma amyloid-beta kinetics may distinguish those with brain amyloidosis. The SILK method is also being generalized to other disease areas including Parkinson’s disease, Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. The next logical step in determining the relationship between blood amyloid-beta kinetics and central nervous system amyloidosis is to determine both in a well-characterized younger population at risk for Alzheimer’s disease.

 

Dr. Bateman has continued investigations on the time based changes in circadian and sleep related Alzheimer’s disease biomarkers and the physiology of CNS amyloid-beta control and processing. His lab’s investigations have led to insights of human circadian patterns of amyloid-beta and soluble APP, and control of the alpha-secretase, beta-secretase, and gamma-secretase processing of amyloid-beta as well as the risk factors of sleep impairment and clearing of brain proteins during sleep.

 

Dr. Bateman is also committed to the efforts of understanding the biological basis of AD and to develop better biomarkers and treatment targets and drugs for improved clinical management. Towards these efforts, his lab has developed methods to quantify the pharmacodynamic action of drugs targeting amyloid-beta, amyloid precursor protein, and Apolipoprotein E. They are currently developing a tau based kinetic assay for drugs which target tau. Dr. Bateman’s lab performed a gamma-secretase inhibitor FDA compliant trial, reported pre-clinical studies of gamma-secretase and beta-secretase inhibitors. Further, they have measured changes in Aβ production in mutation carriers and decreased clearance in sporadic AD. His lab has developed an ApoE SILK method that measures kinetic rates of ApoE in the human CNS and also measuring unbiased measures of ApoE isoforms in human CSF, brain and blood.

 

In Alzheimer’s disease clinical research efforts, Dr. Bateman directed efforts to form the Dominantly Inherited Alzheimer Network (DIAN) Pharma Consortium, the first pharma consortium to support trial design and drug nominations for Autosomal Dominant Alzheimer’s disease, and coordinated with pharmaceutical, regulatory and patient advocacy groups to form the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU). He serves as the director and PI of the DIAN-TU trial, the first multi-drug platform for Alzheimer’s. His efforts are focused on researching both in the lab and through clinical studies the methods to prevent damage and loss of cognitive function by intervening early in the Alzheimer’s disease process.

 

Dr. Bateman also served as the principal investigator of a study on the comprehensive assessment of autosomal dominant Alzheimer disease which was the template for the Dominantly Inherited Alzheimer’s Network (DIAN). DIAN is the largest international study of autosomal dominant Alzheimer’s disease. In his role as the DIAN Clinical Core Leader and Associate Director, he has enjoyed working closely with DIAN sites and assisting with improving recruitment and retention, protocol compliance, quality assurance and quality control measures. The Washington University DIAN site where he serves as site PI has the highest recruitment and retention of participants and completion of assessments in the DIAN network. Dr. Bateman frequently collaborates with other leaders in the DIAN as well as colleagues throughout the world on publications and advisory boards. His research has been recognized with awards from the AlzForum Community, Alzheimer’s Association (Zenith Award), Scientific American, the Glenn Award for Aging Research, and the Metlife Promising Investigator Award.

 

Medical Training

 

Dr. Bateman attended Washington University where he received a B.S. degree in Biology (1995) and a B.S. degree in Electrical Engineering (1995). He attended Case Western Reserve University School of Medicine where he received his M.D. (2000) with special emphasis on the neurosciences. He completed a medical internship (2001) at Barnes-Jewish Hospital followed by Neurology residency (2004) at Washington University in St. Louis. Dr. Bateman then completed post-doctoral research training with David M. Holtzman, M.D. as mentor and clinical research fellowship training at the Washington University ADRC with John Morris, M.D. as mentor. Dr. Bateman treats patients with dementia at the Memory Diagnostic Center of Washington University.

 

Selected Publications

 

Comprehensive PubMed List

 

OECD. Enhancing Translational Research and Clinical Development for Alzheimer’s Disease and other Dementias. OECD Science Technology and Industry Policy Papers 2015. No. 22. doi:10.1787/5jst57jts44-en

 

Monserrate AE, Ryman DC, Ma S, Xiong C, Noble JM, Ringman JM, Morris JC, Danek A, Müller-Sarnowski F, Clifford DB, McDade EM, Brooks WS, Darby DG, Masters CL, Weston PS, Farlow MR, Graff-Radford NR, Salloway SP, Fagan AM, Oliver A, Bateman RJ; for the Dominantly Inherited Alzheimer Network. Factors associated with the onset and persistence of post-lumbar puncture headache. JAMA Neurol. 2015 Jan 26. doi: 10.1001/jamaneurol.2014.3974. [Epub ahead of print] PMID: 25622095. PMCID: PMC4364538

 

Elbert DL, Patterson BW, Bateman RJ. Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans. Math Biosci. 2014 Dec 9. pii: S0025-5564(14)00237-5. doi: 10.1016/j.mbs.2014.11.004. [Epub ahead of print] PMID: 25497960; PMCID: PMC4323682

 

Roberts KF, Elbert DL, Kasten TP, Patterson BW, Sigurdson WC, Connors RE, Ovod V, Munsell LY, Mawuenyega KG, Miller-Thomas MM, Moran CJ, Cross DT 3rd, Derdeyn CP, Bateman RJ. Amyloid-β efflux from the CNS into the plasma. Ann Neurol. 2014 Sep 10. doi: 10.1002/ana.24270. PMID: 25205593. PMCID: PMC4355962

 

Mawuenyega KG, Kasten T, Sigurdson W, Bateman RJ. Amyloid-beta Isoform Metabolism Quantitation by Stable Isotope Labeled Kinetics. Anal Biochem 2013; 440:56-62. PMID: 23714261; PMCID: PMC3749773

 

Wildsmith KR, Basak JM, Patterson BW, Pyatkivskyy Y, Kim, J, Yarasheski KE, Wang JX, Mawuenyega KG, Jiang H, Parsadanian M, Yoon H, Kasten T, Sigurdson WC, Xiong C, Goate A, Holtzman DM, Bateman RJ. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS. PLoS One 2012; 7(6):e38013. Epub 2012 Jun 4. PMID:22675504; PMCID: PMC3366983

 

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; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 2012; 367:795-804. PMID:22784036; PMCID: PMC3474597

 

Huang Y, Potter R, Sigurdson W, Kasten T, Connors R, Morris JC, Benzinger T, Mintun M, Ashwood T, Ferm M, Budd SL, Bateman RJ. Β-Amyloid dynamics in human plasma. Arch Neurol 2012; 69:1591-7. PMID:23229043; PMCID: PMC3808092

 

Portelius E, Zetterberg H, Dean RA, Marcil A, Bourgeois P, Nutu M, Andreasson U, Siemers E, Mawuenyega KG, Sigurdson WC, May PC, Paul SM, Holtzman DM, Blennow K, Bateman RJ. Amyloid-β(1-15/16) as a marker for γ-secretase inhibition in Alzheimer's disease. J Alzheimers Dis 2012; 31:335-41. PMID:22531418; PMCID: PMC6309706

 

Potter R, Patterson BW, Elbert DL, Ovod V, Kasten T, Sigurdson W, Mawuenyega K, Blazey T, Goate A, Chott R, Yarasheski KE, Holtzman DM, Morris JC, Benzinger TLS, Bateman RJ. Increased in Vivo Amyloid-β42 Production, Exchange, and Loss in Presenilin Mutation Carriers. Sci Transl Med 2013; 5, 189ra77 doi: 10.1126/scitranslmed.3005615. PMID: 23761040; PMCID: PMC3838868

 

Mills SL, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, Althage MC, Belyew S, Benzinger TL, Brooks WS, Buckles VD, Cairns NJ, Clifford D, Danek A, Fagan AM, Farlow M, Fox N, Ghetti B, Goate AM, Heinrichs D, Hornbeck R, Jack C, Jucker M, Klunk WE, Marcus DS, Martins RN, Masters CM, Mayeux R, McDade E, Morris JC , Oliver A, Ringman JM, Rossor MN, Salloway S, Schofield PR, Snider J, Snyder P, Sperling RA, Stewart C, Thomas RG, Xiong C, Bateman RJ. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Revue Neurologique 2013; 169(10):737-43; PMID: 24016464; PMCID: PMC3880800.

 

Moulder KL, Snider BJ, Mills SL, Buckles VD, Santacruz AM, Bateman RJ, Morris JC. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther 2013; Oct 17; 5(5):48. [Epub ahead of print]. PMID: 24131566

 

Benzinger TL, Blazey T, Jack CR Jr, Koeppe RA, Su Y, Xiong C, Raichle ME, Snyder AZ, Ances BM, Bateman RJ, Cairns NJ, Fagan AM, Goate A, Marcus DS, Aisen PS, Christensen JJ, Ercole L, Hornbeck RC, Farrar AM, Aldea P, Jasielec MS, Owen CJ, Xie X, Mayeux R, Brickman A, McDade E, Klunk W, Mathis CA, Ringman J, Thompson PM, Ghetti B, Saykin AJ, Sperling RA, Johnson KA, Salloway S, Correia S, Schofield PR, Masters CL, Rowe C, Villemagne VL, Martins R, Ourselin S, Rossor MN, Fox NC, Cash DM, Weiner MW, Holtzman DM, Buckles VD, Moulder K, Morris JC. Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease. Proc Natl Acad Sci U S A. 2013; Nov 19;110(47):E4502-9. PMID:24194552; PMCID: PMC3839740

 

Fagan AM, Xiong C, Jasielec M, Bateman RJ, Goate AM, Benzinger TLS, Ghetti B, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Salloway S, Schofield PR, Sperling RA, Marcus D, Cairns NJ, Buckles VD, Ladenson JH, Morris JC, Holtzman DM. Longitudinal change in CSF biomarkers in Autosomal-Dominant Alzheimer’s disease. Sci Transl Med; 2014; 6:226ra30. PMID: 24598588

 

Castellano JM, Kim J, Stewart FR, Jiang H, Demattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM. Human apoE Isoforms Differentially Regulate Brain Amyloid- Peptide Clearance. Sci Transl Med. 2011 Jun 29;3(89):89ra57. PMC Journal - In Process. PMID#21715678

 

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

 

Zanier ER, Refai D, Zipfel GJ, Zoerle T, Longhi L, Esparza TJ, Spinner ML, Bateman RJ, Brody DL, Stocchetti N. Neurofilament light chain levels in ventricular cerebrospinal fluid after acute aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2011;82(2):157-9. PMID: 20571038. PMID:20571038

 

Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, Salloway S, Sperling RA, Windisch M, Xiong C. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimer’s Res Ther. 2011 Jan 6;2(6):35. PMCID: PMC3109410

 

Hata S, Fujishige S, Araki Y, Taniguchi M, Urakami K, Peskind E, Akatsu H, Araseki M, Yamamoto K, Martins RN, Maeda M, Nishimura M, Levey A, Chung KA, Montine T, Leverenz J, Fagan A, Goate A, Bateman R, Holtzman DM, Yamamoto T, Nakaya T, Gandy S, Suzuki T. Alternative processing of γ-secretase substrates in common forms of mild cognitive impairment and Alzheimer's disease: Evidence for γ-secretase dysfunction. Annals of Neurology 2010; doi: 10.1002/ana.22343. PMID:21681798

 

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. J Neurosci 2010;30:6743-50.

 

Kang J-E, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM. Amyloid-Aβ Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science 2009;326:1005-7.

 

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;66:48-54.

 

Elbert DL, Mawuenyega KG, Scott EA, Wildsmith KR, Bateman RJ. Stable Isotope Labeling Tandem Mass Spectrometry (SILT): Integration with Peptide Identification and Extension to Data-Dependent Scans. J Proteome Res 2008;7:4546-56.

 

Bateman RJ, Klunk WE. Measuring target effect of proposed disease-modifying therapies in Alzheimer's disease. Neurotherapeutics 2008;5:381-90.

 

Bateman RJ, Munsell LY, Chen X, Holtzman DM, Yarasheski KE. Stable Isotope Labeling Tandem Mass Spectrometry (SILT) to Quantify Protein Production and Clearance Rates. Journal of the American Society for Mass Spectrometry 2007;18:997-1006.

 

Bateman RJ, Wen G, Morris JC, Holtzman DM. Fluctuations of CSF amyloid-beta levels: Implications for a diagnostic and therapeutic biomarker. Neurology 2007;68:666-9.

 

Yan P, Hu X, Song H, Yin K, Bateman RJ, Cirrito JR, Xiao Q, Hsu FF, Turk JW, Xu J, Hsu CY, Holtzman DM, Lee JM. Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J Biol Chem 2006.

 

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. Nat Med 2006;12:856-61

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