<< Back

2018 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

C9ORF72 Related Frontotemporal Dementia and Genomic Instability

How might a genetic variation in certain genes lead to the development of frontotemporal dementia?

Rodrigo Lopez Gonzalez
University of Massachusetts Medical School
Worcester, MA - United States


Frontotemporal dementia (FTD) is a group of brain disorders caused by progressive nerve cells loss in specific brain regions. In addition to memory loss, these disorders often result in severe personality changes or problems with language or motor functions.  However, scientists remain uncertain as to exactly how FTDs begin and progress in the brain. Current research indicates that certain types of FTD are linked to a genetic variation of a gene called C9ORF72 that performs an important function of sending and receiving signals between nerve cells.
In preliminary studies, Dr. Rodrigo Lopez-Gonzalez and colleagues have studied how the genetic variation in C9ORF72 may give rise to FTD. Their research involved using nerve cells engineered from special kind of stem cells called induced pluripotent stem cells (iPSCs) - that can be reprogrammed into any cell type in the human body; the iPSCs will be made from adult skin cells of individuals with and without the genetic variations in C90RF72. Dr. Lopez-Gonzalez found that the engineered nerve cells experienced damage to their DNA (genetic material). Further examination found that the genome (or entire set of genes) in these cells showed a large number of genetic variations — a feature known as genomic instability. Such instability may underlie C9ORF72-related damage to the cells and may be a key factor in producing the onset of FTD. 

Research Plan

Dr. Lopez-Gonzalez and colleagues will conduct a study using an improved cell model to investigate how FTD begins in the brain. Their effort will involve a novel cellular model called a brain organoid system. This model, a three-dimensional assembly of cells, enables researchers to explore how disease factors affect both individual cells and the interactions between cells. The researchers will use their system to identify specific types of genomic damage (damage to the DNA) in cells with a genetic variation in C9ORF72, and to determine how that damage may hinder cell-to-cell communication and lead to FTD. 


The results of this study could help clarify the genetic basis of FTD and why changes in this gene link to the brain changes associated with FTD.

Back to Top