Randall J. Bateman, M.D.

Charles F and Joanne Knight Distinguished Professor

Neurosciences Program
Biomedical Informatics and Data Science Program

  • 314-362-3429

  • 107 Biotechnology Building

  • batemanr@wustl.edu

  • http://neuro.wustl.edu/aboutus/facultybiographies/bateman

  • amyloid, apolipoprotein E, Alzheimer’s disease, drug treatment, mass spectrometry, protein production and clearance

  • Alzheimer disease pathophysiology

Research Abstract:

Dr. Bateman’s laboratory focuses on the causes, diagnosis, and future treatments of Alzheimer’s disease (AD). We directly measure the pathology and pathophysiology of AD in humans using multiple techniques.

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 AD. Some of our ongoing projects include:

1) Blood amyloid-beta relationship with amyloid plaques and CSF amyloid-beta: Our lab has developed a highly sensitive and precise mass spectrometry based blood test to detect Alzheimer’s disease amyloid plaques in individuals even before symptom onset. In this project, we aim to determine blood amyloid-beta isoform level relationships to CSF amyloid-beta and amyloid PET, using archived blood samples from cross-sectional and longitudinal studies of cognitively normal, AD, and other neurodegenerative dementias. We are also conducting a clinical study of n=1120 individuals (Study to Evaluate Amyloid in Blood and Imaging Related to Dementia: SEABIRD) recruited from clinics and communities to determine the participant acceptability and validity of the blood Aβ test as a screening test for brain amyloidosis.

2) Evaluation of plasma tau and phospho-tau quantitation by mass spectrometry as biomarkers for differential diagnosis of AD and tauopathies: This project aims to develop and assess mass spectrometry based methods measuring tau isoforms in plasma as biomarkers for AD. We hypothesize that specific changes in the tau protein will be detectable in plasma and will significantly improve the diagnostic power of blood based biomarkers for AD. This project will also pave the way for evaluating plasma tau isoforms as biomarkers in other tauopathies. Studies in cerebrospinal fluid by our lab have demonstrated multiple sequential changes of phospho-tau species that link amyloid to future tau aggregation.

3) CNS tau kinetics in Alzheimer’s disease and other tauopathies: The goal of this study is to characterize tau kinetics and tau aggregation in the human central nervous system and to test the hypothesis that tau kinetics are altered (e.g., increased production, decreased clearance, and increased aggregation rate) with normal aging and in AD and non-AD tauopathies. Results will inform scientists and clinicians about how tau changes in the human brain over time and to what extent, and will be important in effectively designing future clinical trials to treat AD and other tauopathies by targeting tau. Initial findings show increased tau production associated with amyloid plaques.

4) Assessing the added diagnostic value of peripheral apolipoprotein E (ApoE) protein levels to current blood-based assays for CNS amyloidosis: This study proposes to determine the relationship between peripheral ApoE concentrations and CNS amyloidosis, and plasma ApoE glycoform levels and CNS amyloidosis.

5) Characterization of neurofilament light chain in AD and other neurodegenerative disorders: The goal of this project is to develop a mass spectrometry assay to characterize and measure neurofilament light chain (NfL) isoforms, a biomarker of neurodegeneration, in human blood.

6) Stable isotope labeling & quantitative mass spectrometry imaging of Alzheimer’s disease pathology in human brain: Our goal is to measure, for the first time in human AD brain, the metabolism of neurons, how they are affected by AD, and if this is directly related to amyloid and tau accumulation inside the neuron affecting function and overall health.

Selected Publications:

Blood amyloid-beta relationship with amyloid plaques and CSF amyloid-beta project:
a. SEABIRD study website: https://sites.wustl.edu/seabird/"

b. Blood test publication: Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C, Fagan AM, Bateman RJ. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019 Oct 22;93(17):e1647-e1659. doi: 10.1212/WNL.0000000000008081. Epub 2019 Aug 1. PMID: 31371569; PMCID: PMC6946467. https://pubmed.ncbi.nlm.nih.gov/31371569/

c. Alzforum blood test press release: https://www.alzforum.org/news/conference-coverage/finally-blood-test-alzheimers"

d. GatesNotes blog: https://www.gatesnotes.com/Health/The-unexpected-way-we-might-one-day-diagnose-Alzheimers

Evaluation of plasma tau and phospho-tau quantitation by mass spectrometry as biomarkers for differential diagnosis of AD and tauopathies project:
a. Barthelemy 2020 plasma tau publication: Barthélemy NR, Horie K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer's disease. J Exp Med. 2020 Nov 2;217(11):e20200861. doi: 10.1084/jem.20200861. PMID: 32725127. https://pubmed.ncbi.nlm.nih.gov/32725127/

b. Alzforum plasma tau press release:https://www.alzforum.org/news/conference-coverage/blood-tests-phospho-tau-av42-track-brain-amyloid

c. Barthelemy/McDade 2020 CSF phospho-tau publication: Barthélemy NR, Li Y, Joseph-Mathurin N, Gordon BA, Hassenstab J, Benzinger TLS, Buckles V, Fagan AM, Perrin RJ, Goate AM, Morris JC, Karch CM, Xiong C, Allegri R, Mendez PC, Berman SB, Ikeuchi T, Mori H, Shimada H, Shoji M, Suzuki K, Noble J, Farlow M, Chhatwal J, Graff-Radford NR, Salloway S, Schofield PR, Masters CL, Martins RN, O'Connor A, Fox NC, Levin J, Jucker M, Gabelle A, Lehmann S, Sato C, Bateman RJ, McDade E; Dominantly Inherited Alzheimer Network. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. Nat Med. 2020 Mar;26(3):398-407. doi: 10.1038/s41591-020-0781-z. Epub 2020 Mar 11. PMID: 32161412; PMCID: PMC7309367. https://pubmed.ncbi.nlm.nih.gov/32161412/

d. Alzforum CSF phospho-tau press release:

CNS tau kinetics in Alzheimer’s disease and other tauopathies project:
a. Sato/Barthelemy 2018 tau kinetics publication: Sato C, Barthélemy NR, Mawuenyega KG, Patterson BW, Gordon BA, Jockel-Balsarotti J, Sullivan M, Crisp MJ, Kasten T, Kirmess KM, Kanaan NM, Yarasheski KE, Baker-Nigh A, Benzinger TLS, Miller TM, Karch CM, Bateman RJ. Tau Kinetics in Neurons and the Human Central Nervous System. Neuron. 2018 Mar 21;97(6):1284-1298.e7. doi: 10.1016/j.neuron.2018.02.015. Erratum in: Neuron. 2018 May 16;98 (4):861-864. PMID: 29566794; PMCID: PMC6137722. https://pubmed.ncbi.nlm.nih.gov/29566794/

b. Alzforum tau kinetics article:https://www.alzforum.org/news/research-news/isotope-labeling-links-tau-production-av-burden

Stable isotope labeling & quantitative mass spectrometry imaging of Alzheimer’s disease pathology in human brain project:
a. Wildburger 2018 publication: Wildburger NC, Gyngard F, Guillermier C, Patterson BW, Elbert D, Mawuenyega KG, Schneider T, Green K, Roth R, Schmidt RE, Cairns NJ, Benzinger TLS, Steinhauser ML, Bateman RJ. Amyloid-β Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity. Front Neurol. 2018 Mar 22;9:169. doi: 10.3389/fneur.2018.00169. PMID: 29623063; PMCID: PMC5874304. https://pubmed.ncbi.nlm.nih.gov/29623063/

Last Updated: 10/6/2020 9:16:04 AM

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