Clarifying the Role of the ABCA7 Gene on Alzheimer’s Risk

Holly Cukier, PhD
University of Miami, Miller School of Medicine (Coral Gables, FL)

Co-Principal Investigators

Derek Dykxnoorn, PhD
University of Miami (Coral Gables, FL)
Year Awarded:
Grant Duration:
July 1, 2018 to June 30, 2021
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Southeastern
Holly Cukier, PhD

Elucidating the Cell-Specific Roles of ABCA7


Alzheimer’s disease (AD) occurs more frequently in diverse populations (ie: African Americans and Hispanics) than in white populations. This proposal seeks to investigate the role of a gene shown to be a risk factor for AD, ABCA7, and the consequence of a mutation that was first identified in African Americans. Stem cell lines have been generated from African Americans with this deletion and both neurons and cells involved in immunity, microglia, will be created. Using these two cell types, we will investigate how this deletion may affect the normal way neurons and microglia develop, and how that may lead to AD.


We hope to better understand the role that a deletion that we recently identified in ABCA7, a gene implicated in Alzheimer's disease (AD) across populations, plays in the development of AD. The deletion was first identified in African Americans (AA), who comprise an underserved population, and the deletion appears to be of African origin. Since ABCA7 is expressed in a variety of cell types, we will we will generate both neurons and microglia, support cells to the neurons, from stem cell lines of AD patients with the ABCA7 deletion, as well as control stem cells lacking the deletion. Both the neurons and microglia will be functionally characterized for cellular and morphological features, as well as for AD-specific features. We will then combine the neurons and microglia (control neurons with AD microglia and vice versa) to determine whether one cell type contributes more to the AD specific phenotypes, or if there is a synergistic effect between the two cell types. We aim to determine if this deletion is sufficient to induce AD pathogenesis, as well as gain a greater insight into ABCA7, a gene implicated in AD across populations. The ultimate goal is to determine whether ABCA7 is a suitable target for the development of novel AD therapeutics.

About the Researcher

Dr. Cukier is a research assistant professor in the Departments of Neurology and Human Genetics at the University of Miami, Miller School of Medicine, as well as the associate director for the Induced Pluripotent Stem Cell Core at the John P. Hussman Institute for Human Genomics. She is an alumna of the University of Miami, where she graduated with honors. Dr. Cukier received her doctoral degree in 2007 from Baylor College of Medicine in the Department of Human and Molecular Genetics, where she generated a novel fruit fly model of Rett syndrome, a disorder on the autism spectrum, and was awarded a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health. Dr. Cukier returned to the University of Miami and currently studies the genetics underlying autism spectrum disorders and Alzheimer’s disease. Dr. Cukier studies families with these diseases, as well as examines minority populations for potential genetic differences. Furthermore, she is engaged in generating patient-specific induced pluripotent stem cell lines to study the course of disease pathogenesis.

Personal Story

My initial interest in human genetics sprang from learning in high school about the discovery of the genetic defect that cause Huntington's disease. I found the field fascinating and heavy with untapped potential. Since that time, the human genome has been sequenced and the field has exploded with discoveries in the genetics underlying both common and rare disorders. More recently, stem cell models have also emerged as a tool to investigate the effects that these genetic defects have on disease-relevant cell types. I study two common neurological diseases, Alzheimer's disease (AD) and autism spectrum disorders (ASD), as I feel that this work has the potential to help a large number of people. Each day, I am eager to use these ground-breaking methods to learn more about the genetics underlying AD and ASD, and hopefully, how they might be ameliorated. I greatly appreciate the support that the BrightFocus Foundation is providing to allow my research in AD to continue.

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