David M. Holtzman

Holtzman is currently Professor of Neurology, scientific director of the Hope Center for Neurological Disorders, and associate director of the Knight Alzheimer's Disease Research Center at Washington University School of Medicine. He stepped down from his position as department chairman in 2021.  The Holtzman Lab is dedicated to exploring the biological mechanisms underlying neurodegeneration. Holtzman's work has studied mechanisms by which apoE, amyloid beta, and tau metabolism are implicated in neurodegeneration in the context of Alzheimer's disease. Holtzman is also a co-founder of C2N Diagnostics, LLC. Holtzman and his former trainee, Randall Bateman, developed C2N Diagnostics in 2007 with the goal of increasing the understanding the molecular mechanisms underlying neurological diseases through measurements of concentration and metabolism of CNS-derived biomolecules.

In 2001, Holtzman and his team published a paper showing that administration of the anti-Aβ antibody (m266) in mice changes the equilibrium of Aβ across the CNS and blood plasma leading to increased Aβ sequestration in plasma which reduces the burden of Aβ in the brain. This antibody, m266, was licensed to Eli Lilly and humanized.  Using the humanized anti-Aβ antibody, Solanezumab, Eli Lilly began a series of clinical trials to discern the therapeutic potential of anti-Aβ immunotherapy in humans with AD. Results of these trials were disappointing. Solanezunmab treatment did not meet the primary endpoint of the clinical trials in mild AD, however, a clinical trial known as A4 in “presymptomatic” AD is still ongoing. Holtzman's lab has also focused on anti-tau immunotherapeutic approaches to treating AD, and this approach is now in phase II clinical trials following licensing of an anti-tau antibody his lab developed with AbbVie.

In 1994, Holtzman became an assistant professor at Washington University in St. Louis. By 2002, Holtzman was promoted to Associate Professor of Neurology, and by 2003, he was promoted to Full Professor in the Departments of Neurology and Developmental Biology at Washington University. In 2003, he also became the Chairman of the Department of Neurology, and in 2015 he became the Scientific Director of the Hope Center for Neurological Disorders.

After completing his MD, Holtzman pursued a residency in Neurology at the University of California, San Francisco (UCSF) from 1985 to 1989. Following his residency, he completed his postdoctoral research under the mentorship of William C. Mobley at UCSF from 1989 to 1994. His postdoctoral research focused on developing mouse models of neonatal stroke and neurodegeneration as well as elucidating the role neurotrophins play in modulating neuronal activity.

Holtzman was born in St. Louis, Missouri. Holtzman pursued a six-year combined Bachelor's and Medical Degree at Northwestern University in Evanston, Illinois. He obtained his Bachelors of Science in Medical Education in 1983 and his Medical Degree in 1985.