In an article published in the Journal of Clinical Investigation, David Holtzman, a member of the Cure Alzheimer’s Fund Research Leadership Council, reported the discovery of a novel antibody against APOE called HAE-4 that reduced amyloid beta by half in a mouse model for Alzheimer’s disease.
APOE plays a critical role in transporting cholesterol in the body. APOE variants are the largest single risk factor for Alzheimer’s disease. Because HAE-4 reduces amyloid beta levels without disrupting the levels of APOE in the blood, its discovery marks a critical moment in the field of Alzheimer’s research. According to Dr. Holtzman, “it turns out that APOE in the plaques has a different structure than the form of APOE found in the blood.” The fact that this novel antibody can recognize and clear APOE from the brain and not the blood makes it a powerful target for future clinical trials.
Science Daily: “Antibody Removes Alzheimer’s Plaques, in Mice https://www.sciencedaily.com/releases/2018/03/180326161000.htm
Washington University School of Medicine in St. Louis
“Antibody removes Alzheimer’s plaques, in mice.” https://medicine.wustl.edu/news/antibody-removes-alzheimers-plaques-via-apoe-mice/
The original paper is available here: https://www.jci.org/articles/view/96429
Photo: ApoE4 is the strongest genetic risk factor for Alzheimer’s disease (AD) and strongly influences amyloid plaque aggregation. Targeting the degradation of apoE in plaques could offer a better disease-modifying therapy for AD. This image depicts anti-apoE antibody HAE-4 (red) binding to the core of amyloid plaques (blue) in human AD brain tissue.
(Credit: Monica Xiong, Ph.D. student, Holtzman Lab)