Researchers from Baylor College of Medicine are set to begin the data analysis phase of a project to discover genetic markers that can be used to diagnose or establish risk factors for Alzheimer's disease.

"Although large genetic studies with Alzheimer's disease have been conducted and are ongoing, we will likely be one of the first ones looking at the role of copy number variations in Alzheimer disease," said Dr. Kinga Szigeti, an assistant professor of neurology and molecular and human genetics at BCM.

Consortium efforts

Five institutions in Texas teamed up to achieve the sample sizes needed for genetic studies in Alzheimer disease. The consortium includes BCM, The University of Texas Southwestern Medical Center, Texas Tech University Health Science Center, The University of North Texas Health Science Center at Fort Worth and The University of Texas Health Science Center at San Antonio.

Approximately 5.3 million Americans are living with Alzheimer's disease. It occurs when healthy brain tissue deteriorates over time, slowly destroying cognitive function (thinking, remembering and reasoning). There are no current cures for the disease, but there are treatments to slow down the deterioration and medications to help with quality-of-life issues, such as increased paranoia and anxiety.

In the data analysis phase of the project, Szigeti said the BCM group will look for duplications and deletions in the sequence (known as copy number variations) across complete sets of genomes to find variations associated with earlier onset of the disease. "We hope to find modifiable genetic risk factors that can delay onset of the disease by several years."

To get to this phase, the consortium enrolled eligible patients, conducted neuropsychological testing and collected DNA samples. The samples are being processed through microarray technology. The analysis phase is expected to take several months, Szigeti said.

Different approach

BCM's approach differs from ongoing studies that have focused on single base changes (known as single nucleotide polymorphisms, or SNPs).

Just recently, the SNPs approach has helped researchers identify three new genes (CLU or clusterin, PICALM, and CR1 or Erythrocyte complement receptor 1) that may be associated with Alzheimer's disease, Szigeti said.

Another gene, the APOE gene, has been shown consistently to be associated with Alzheimer's disease.

"There is suggestive evidence that these genes decrease amyloid beta clearance in the brain," said Szigeti. "It is hypothesized that Alzheimer's disease develops when there is accumulation of amyloid beta in the brain, resulting in neurodegeneration."

"For a small fraction of Alzheimer disease there is a genetic cause, for which we can perform testing. These are the families where three generations are affected and the symptoms start young, typically before age 60," said Szigeti. "However, for the majority of patients there is no genetic test. The identified risk factors do not mean that somebody will get the disease, only increases the chance."

Targeting neurodegeneration

These research efforts are important because they can provide valuable insight into the mechanism of the disease and suggest drug targets, said Szigeti.

The BCM group in collaboration with the consortium will be focused on unraveling clues about these mechanisms, Szigeti said. "Ultimately, we hope to identify the most prominent pathways and target mechanisms that lead to neurodegeneration."

Risk factors

Other BCM researchers involved in the project include Drs. Rachelle Doody and Susan Rountree, both of the Alzheimer's Disease and Memory Disorders Center at BCM.

"With Alzheimer's disease, it's harder to elucidate the players that concert the risk because of its relationship with aging and the large number of genetic variables," said Szigeti. "Progress is being made, but putting all the pieces of the puzzle together will need concerted efforts in the years to come."

Nothing can be done yet to alter the development of the disease, but Szigeti recommended modifying associated risk factors.

Those modifications include:

  • Lowering cholesterol
  • Reducing high blood pressure
  • Managing diabetes
  • Implementing a healthy exercise program