David M. Holtzman, MD

Head of the Department of Neurology

Washington University in St. Louis (WU)

The lab of Dr. David Holtzman focuses on Alzheimer’s disease, in particular understanding the metabolism of the amyloid-beta peptide in the CNS and plasma. The Holtman lab has demonstrated how endogenous and exogenous Abeta binding molecules play key roles in Alzheimer’s disease (AD) pathogenesis. Utilization of transgenic and knockout mice has demonstrated that apoE and a molecule called apoJ/clusterin play critical roles in vivo in the formation of amyloid and its toxicity and that apoE4 is most likely an AD risk factor via its effects on Abeta conformation and toxicity. Recent work with anti-Abeta antibodies demonstrates a novel mechanism in which antibodies can act as an “Abeta sink” in the plasma and has exciting potential to lead to new diagnostic and treatment methods for AD. More recently, the lab is attempting to identify antecedent biomarkers for AD, particularly in human CSF.