Discovery of Dementia-Related Genes is Key Step in Finding Therapies


More than 5 million people in the United States have Alzheimer’s disease or related dementias. The U.S. Centers for Disease Control and Prevention (CDC) say that figure is likely to triple by 2060. Currently no treatment can alter the course of dementia associated with the death of brain cells (neurodegeneration).

Dementia Genes Linked to Buildup of Tau Proteins

While scientists have previously identified genes associated with dementia risk, they don’t have much understanding of how those genes contribute to neurodegeneration. But UCLA researchers are one step closer to effective dementia treatments after discovering two major groups of genes linked to dementia.

Mutations in the identified gene clusters may lead to increased production of the protein known as tau. A buildup of tau proteins tangled inside brain cells is a hallmark of dementia.

Genetic Processes Result in Neurodegeneration

Using an approach known as systems biology, researchers studied the genome by taking into account the interactions of genes plus the cells and proteins they produce. As a result, they:

  • Identified the genetic processes of the mutations that caused excess tau in frontotemporal dementia, a type of early-onset dementia that has a strong genetic component.
  • Used three genetically different types of mice to study the mutations. They found two gene clusters susceptible to neurodegeneration in regions of the brain that are also susceptible.
  • Performed additional experiments to confirm the same genetic process occurs in human brains.

Targeting Gene Clusters Holds the Future for Dementia Treatments

The research team then searched a database of experimental drugs to identify ones that might interfere with neurodegeneration. They found one of the molecules in experimental medications interfered with the loss of brain cells.

These findings are a first step to developing drugs that can target the gene clusters tied to the overproduction of tau protein, thereby slowing or stopping dementia progression.

Learn more about this remarkable discovery by UCLA Health researchers at the Semel Institute for Neuroscience and Human Behavior.