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2018 Alzheimer's Association Research Fellowship (AARF)

ApoE isoform effects on tau pathology using iPSC-derived cortical organoids

How do different variations of the APOE gene lead to abnormal tau accumulation in the brain, in Alzheimer’s?

Jing Zhao, Ph.D.
Mayo Clinic Jacksonville
Jacksonville, FL - United States


The three types of apolipoprotein E (APoE-e2, APoE-e3, and APoE-e4) play important roles in the human body, but the APoE-e4 form has been linked to Alzheimer’s and dementia with Lewy bodies.  APoE-e4 has been shown to stimulate accumulation of the protein fragment beta-amyloid in the brain- a hallmark of Alzheimer’s.  It is unclear how the different variations of the APOE gene affect another hallmark of Alzheimer’s, the aggregation of an abnormal form of the tau protein into tangles in the brain. New tools are needed to help researchers investigate the changes that occur in the brain in Alzheimer’s disease, such as the effects of different APOE forms on tau accumulation.

Research Plan

Dr. Jing Zhao developed a new experimental system that can help researchers understand the molecular changes that happen in the brain during the development of Alzheimer’s. Dr. Zhao uses special type of cells, called the human inducible pluripotent stem cells (or iPSCs) grown on a laboratory dish, with the potential to grow into any type of cell in the human body.
Dr. Zhao used these special cells to create small collections of cells that act like human brain tissue. The researchers used a cutting-edge molecular tool to insert specific versions of the APOE gene and abnormal tau forms into the special cells. Using this technique, Dr. Zhao will investigate how each version of the APOE gene, affects the accumulation of abnormal tau proteins and the formation of tangles.


This study will not only lead to a better understanding of the link between versions of the APOE gene and abnormal form of the tau protein, in Alzheimer’s and other dementias, but also provide the research community with a new tool that can be used to study the various changes that occur in the brain during the development of Alzheimer’s. If successful, the study outcomes could advance the field of Alzheimer’s by giving rise to a novel model that allows researchers to study the progression of Alzheimer’s and identifying therapeutic targets.

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