Genes Tied to Dementia Identified, May Lead to New Therapies

Scientists have identified genetic processes involved in the neurodegeneration that occurs in dementia, an important step towards developing therapies that could slow or halt the course of the disease.

Researchers from the University of California, Los Angeles (UCLA) in the US discovered two major groups of genes involved in mutations that result in an overproduction of a protein called tau, a hallmark of the progressive loss of neurons seen in major forms of dementia.

The study, published in the journal Nature Medicine, was largely done in mouse models of dementia, although the researchers performed additional experiments that indicated the same genetic process occurs in human brains.

The team searched a large database of the genetic effects of experimental drugs to identify those that might alter this loss of neurons, also called neurodegeneration.

In human cell cultures, the researchers showed that the use of these molecules interfered with neurodegeneration.

Our study is the most comprehensive published effort to date to identify the source of neurodegeneration across species and provides an important roadmap for the development of potentially effective new drugs for Alzheimer’s disease and other dementia.

Daniel Geschwind, professor at UCLA

There is currently no treatment that can alter the course of neurodegeneration associated dementia, researchers said.

Although scientists have identified genes associated with dementia risk, there is little understanding of how those genes contribute to the cascade of events that lead brain cells to die.

The team sought to solve that puzzle through an approach known as “systems biology” which applies powerful genomic and analytic tools to studying the genome holistically. It takes into account the complex interactions of the thousands of genes and the cells and proteins they produce.

The researchers used systems biology to identify genetic processes in a mutation that results in the overproduction of tau in frontotemporal dementia, a form of early-onset dementia.

A similar process has been shown to play an important role in Alzheimer’s disease and another form of dementia known as supranuclear palsy, which affects both movement and cognition.

The team hypothesised that a reason why research with mouse models of dementia often fails to produce results translatable to humans is that most mouse studies have relied on a single inbred strain.

To increase the likelihood that their findings would have broader implications, the researchers studied the mutation caused by frontotemporal dementia in three genetically distinct strains of mice.

The team looked at the genetic activity occurring in different parts of a degenerating brain.

In the study, two gene clusters were found to be associated with neurodegeneration across all three mouse models and in the susceptible regions of the brain.