USC lab links genetic mutation to Alzheimer’s

A team of USC researchers led by Paul Thompson, director of the USC Imaging Genetics Center, published  findings that Alzheimer’s patients are affected by the disease three years earlier than expected.

Their work, which was published in last week’s edition of The New England Journal of Medicine, goes into depth about carriers of the TREM2 gene variant, a genetic mutation that was linked to Alzheimer’s earlier this year. This edition of the journal, also included five other studies focusing on the TREM2 gene variant.

“You can study all kinds of factors like exercise, diet, medication and even stress. This study is a little different, where you search through your DNA and find spelling errors or mutations that increase your risk of Alzheimer’s,” Thompson said. Besides his role as director, Thompson is also a professor of neurology, psychiatry, radiology, engineering and ophthalmology, as well as an associate director of the Institute for Neuroimaging and Informatics.

The study’s co-authors include postdoctoral researcher Priya Rajagopalan and assistant professor Derrek Hibar of the USC Imaging Genetics Center, where a team of more than 30 researchers worked on the project. Thompson and his colleague Arthur Toga moved from UCLA to USC this fall, bringing the Laboratory of Neuro Imaging and their work on brain mapping and neuroimaging diseases such as Alzheimer’s, schizophrenia and depression, with them.

“We’ve been tracking the disease for some time and one question that we studied is what it is that slows Alzheimer’s, and what is it that speeds it up and if there’s anything we can do to resist the illness,” Thompson said.

The Imaging Genetics Center was specifically working on researching Alzheimer’s disease for 20 years before this breakthrough, Thompson said.

The TREM2 gene variant is a gene mutation carried by 1 percent of the population. By mapping the effects of genetic mutation with brain magnetic resonance imaging scans, the lab became the first to show how this Alzheimer’s risk factor affects a living human brain.

Through the Alzheimer’s Disease Neuroimaging Initiative, the study recruited 478 adults from North America, 100 of whom had Alzheimer’s disease, 221 who had mild cognitive impairment and 157 healthy elderly adults. The study showed a dramatic loss in brain tissue. In comparison to the less than 1 percent per year rate of healthy people, which is also offset by normal tissue generation from mental stimulation, the carriers of TREM2 lose about 3 percent of their brain tissue per year. Alzheimer’s occurs when approximately 10 percent of brain tissue has eroded.

Thompson clarified the benefits of the study. The discovery can significantly speed up drug trials. According to Thompson, if there is a new successful Alzheimer’s medication that needs drug trials, people won’t have to wait three to four years for the brain to degenerate, and the results will be more apparent.

“Also, it gives us a lot of understanding about what Alzheimer’s disease is,” Thompson said. “We used think that Alzheimer’s comes from senile plaques, building up in your brain, and basically clogging up your brain. That is certainly true, but the people carrying this risk gene have a problem with inflammation in their brain.”

This connection could aid in the development different kinds of anti-inflammatory treatments that might ameliorate the condition of patients suffering from Alzheimer’s, even though there still isn’t a cure.

Some students said they weren’t sure how the study could positively impact current Alzheimer’s patients.

“I understand that finding this gene mutation that causes the brain to degrade the brain faster is a breakthrough, but I don’t feel as though it is that helpful because there is currently no cure for Alzheimer’s,” said Tiffany Tse, a sophomore majoring in biological sciences.

Other students were optimistic about the results of the study.

“Even though there’s no way to eradicate it yet, I definitely think this is an optimistic step in the right direction that might eventually lead to greater onset prevention,” said Helen Chou, a sophomore majoring in neuroscience.

Many were impressed that USC was the first to make these discoveries.

“I think they discovered something important that could be used in innovative treatments for Alzheimer’s, and it’s that much more important because of how it’s one of the first research projects that has shown these results,” said Sandy Lin, a sophomore majoring in human biology.

Currently, Thompson’s team is working on ways of bettering the lives of Alzheimer’s patients.

“Things like staying fit and rigorous cardiovascular activity can protect the brain as we age, but what we want to know is, how much exercise?” he said. “Or can you achieve the results … through other forms of stimulation like education?”