Early Risk of Alzheimer's May Be Identified by Combining DTI-MR Brain Imaging and Genetic Analysis

A new study has found evidence suggesting that a variation of a specific gene may play a role in late-onset Alzheimer's disease (AD). This novel study has combined genetics and brain imaging to determine which people may be at risk for developing late-onset AD long before symptoms are evident.

The gene, which is called brain-derived neurotrophic factor (BDNF), is critical to maintaining healthy function of the brain, primarily the brain's memory center of the hippocampus and entorhinal cortex, and is responsible for learning and memory function. Past research has found that less BDNF is present in the memory center of those diagnosed with AD. However, genetic association studies alone have not generated definite findings regarding this gene. Instead, a combination of genetics and brain imaging were used to demonstrate distinct effects of this gene in the brain.

In the study, conducted by investigators from the Center for Addiction and Mental Health (CAMH; Toronto, Ontario, Canada) and published in the February 2011 issue of the journal Archives of General Psychiatry, a variation of the BDNF gene called val66met, was monitored, and examined in healthy individuals to see what effect it had on the brain. Genotyping was used to determine which study participants carried the gene variation. Then two types of brain imaging, high-resolution magnetic resonance imaging (MRI) cortical thickness mapping, and diffusion tensor imaging (DTI), were applied to measure the physical structures of the brain in each individual. This combination of genetic screening and imaging showed that BDNF val66met gene variation influenced precisely those brain structures and connections that degrade at the earliest phases of AD.

"Our sample consisted of healthy adults who passed all cognitive testing and displayed no clinical symptoms of Alzheimer's disease, yet the brains of those who carried the gene variation had differences in their brain structures consistent with changes we see in people at the earliest stages of Alzheimer's disease,” said Dr. Aristotle Voineskos, physician and scientist at CAMH, and lead investigator of the study.

Participants who carried the variation were more apt to have thinner temporal lobe structures and disrupted white matter tract connections leading into the temporal lobe--the same structures and neural networks that have deteriorated in the brains of Alzheimer's patients when their brains are examined postmortem.

"In the past, Alzheimer's disease could only be diagnosed and treated once outward symptoms became present,” added Dr. Voineskos. "Early identification is key because, in addition to seeking therapeutic treatments early to reduce suffering, delaying Alzheimer's onset by only two years has the potential of saving the Canadian health care system nearly [US]$15 billion over the next 10 years. The combination of brain imaging and genetics is a key approach that may help us to identify people at risk for Alzheimer's disease.”

This advance in image-genetics research, according to the scientists, can be valuable in the study of other brain disorders and will enable researchers to examine how a gene affects the brain and possibly intervene before an individual develops an illness.

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Center for Addiction and Mental Health