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Ancient DNA can both diminish and defend modern minds from Alzheimer’s

Genetic mutations that once helped may be mismatched in a modern environment.
January 3, 2017

ASU researcher leads new study showing cognitive decline may be influenced by interaction of genetics and parasites

You’ve likely heard about being in the right place at the wrong time, but what about having the right genes in the wrong environment? In other words, could a genetic mutation (or allele) that puts populations at risk for illnesses in one environmental setting manifest itself in positive ways in a different setting?

That’s the question behind a recent paper published in The FASEB Journal by several researchers including lead author Ben Trumble, an assistant professor at Arizona State University’s School of Human Evolution and Social Change and ASU’s Center for Evolution and Medicine.  

These researchers examined how the apolipoprotein E (ApoE) gene might function differently in an infectious environment than in the urban industrialized settings where ApoE has mostly been examined. All ApoE proteins help mediate cholesterol metabolism and assist in the crucial activity of transporting fatty acids to the brain. But in industrialized societies, ApoE4 variant carriers also face up to a four-fold higher risk for Alzheimer’s disease and other age-related cognitive declines, as well as a higher risk for cardiovascular disease.

The goal of this study, Trumble explained, was to reexamine the potentially detrimental effects of the globally present ApoE4 allele in environmental conditions more typical of those experienced throughout our species’ existence — in this case, a community of Amazonian forager-horticulturalists called the Tsimane. 

“For 99 percent of human evolution, we lived as hunter-gatherers in small bands, and the last 5,000-10,000 years — with plant and animal domestication and sedentary urban industrial life — is completely novel,” Trumble says. “I can drive to a fast-food restaurant to ‘hunt and gather’ 20,000 calories in a few minutes or go to the hospital if I’m sick, but this was not the case throughout most of human evolution.”

Due to the tropical environment and a lack of sanitation, running water or electricity, remote populations like the Tsimane face high exposure to parasites and pathogens, which cause their own damage to cognitive abilities when untreated.

As a result, one might expect Tsimane ApoE4 carriers who also have a high parasite burden to experience faster and more severe mental decline in the presence of both these genetic and environmental risk factors.

But when the Tsimane Health and Life History Project tested these individuals using a seven-part cognitive assessment and a medical exam, they discovered the opposite.

“It seems that some of the very genetic mutations that help us succeed in more hazardous time periods and environments may actually become mismatched in our relatively safe and sterile post-industrial lifestyles.” 

— Ben Trumble, ASU assistant professor

In fact, Tsimane who both carried ApoE4 and had a high parasitic burden displayed steadier or even improved cognitive function in the assessment vs. non-carriers with a similar level of parasitic exposure. The researchers controlled for other potential confounders like age and schooling, but the effect still remained strong. This indicated that the allele potentially played a role in maintaining cognitive function even when exposed to environmental-based health threats.

For Tsimane ApoE4 carriers without high parasite burdens, the rates of cognitive decline were more similar to those seen in industrialized societies, where ApoE4 reduces cognitive performance.

“It seems that some of the very genetic mutations that help us succeed in more hazardous time periods and environments may actually become mismatched in our relatively safe and sterile post-industrial lifestyles,” Trumble said.

Still, the ApoE4 variant appears to be much more than an evolutionary leftover gone bad, he added. For example, several studies have shown potential benefits of ApoE4 in early childhood development, and ApoE4 has also been shown to eliminate some infections like giardia and hepatitis.

“Alleles with harmful effects may remain in a population if such harm occurs late in life, and more so if those same alleles have other positive effects,” said co-author Michael Gurven, professor of anthropology at University of California, Santa Barbara. “Exploring the effects of genes associated with chronic disease, such as ApoE4, in a broader range of environments under more infectious conditions is likely to provide much-needed insight into why such ‘bad genes’ persist.”

Chronic diseases of aging are extremely costly to treat. In fact, according to the Alzheimer’s Association, if left unchecked, this particular illness is expected to cost the U.S. alone more than $1 trillion by 2050.

However, Trumble's team will continue to examine how environmental conditions interact with our immune system and our genes, in the hopes that other scientists might one day be able to prevent these diseases or create new kinds of medical treatments.

The abstract and full research paper “Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden” can be viewed here in The FASEB Journal.

Aaron Pugh

Manager of Marketing and Communications , School of Human Evolution and Social Change

480-727-6577

 
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ASU radio show gives voice to veterans

Cronkite student hosts radio show to change narrative about military vets.
'Veterans Diaries' airs each Wednesday on ASU AM radio station The Blaze.
January 3, 2017

Cronkite junior Chris Cadeau uses experience, platform to break stereotypes that surround returning soldiers

Arizona State University junior Christopher Cadeau wants to help change the narrative that veterans are either homeless or heroes, and he has created a radio show dedicated solely to telling more diverse stories of the people who’ve served.

Veterans Diaries” wrapped its first season last month on KASC-The Blaze, ASU’s AM radio station.

A 30-year-old sports journalism major at the Walter Cronkite School of Journalism and Mass Communication, Cadeau said was pleased with the results of his first semester behind the microphone. He is also pushing to get better. 

“Honestly, I’m never satisfied, and it’s hard for me to accept praise,” said Cadeau, whose background includes eight years in the Marines. He also has five years of recovery.

“I once asked my sponsor, ‘When does this chip on my shoulder go away? When am I going to be OK with where I am in my life?’”

That chip developed as a young child growing up in Canton, Michigan, Cadeau said. He cites his parents’ divorce at age 4 and the rape of a sibling as the first of several emotional blows. As a teen, Cadeau got into trouble with the law and embraced drugs and alcohol. He knew the Marines could turn his life around.

“I was very street smart and good at evaluating pros and cons,” Cadeau said. “The pros were: You’re going to leave this situation; you’re going to get three meals a day; you’re going to have a career.”

He said the cons were just as clear. “If you stay here, you will go to jail.”

Cadeau said he joined the Marines in 2006 and ended up as a fighter jet mechanic, working on F-18s in Miramar, California, near San Diego. He transitioned back into civilian life and took advantage of his GI Bill benefits, eventually being accepted into ASU in December 2015.

He wanted to pursue sports journalism after a heartfelt discussion with a sponsor in his recovery program.

“My sponsor asked, ‘What do you love to do?’ I told him I love sports journalism and have always been infatuated with it,” Cadeau said. “If you add up all the hours I’ve spent in sports from the moment I come home to the time I’m on my smartphone looking up results, I need to find a way to get paid for this.”

He also called ASU’s Pat Tillman Center for Veterans and spoke to Joanna Sweatt, a former military advocate at the center. Cadeau said her first words were, “Everything’s going to be OK.”

Sweatt recruited Cadeau for the center’s work-study program. He currently works for the center’s outreach team, led by Matt Schmidt.

“We’re always trying to find new ways to engage student vets, and because Chris is a journalism major, the idea of a radio show came naturally,” said Schmidt, a recruitment specialist. “Chris is a natural leader and saw this not only as a challenge, but as way to impact lives and change the narrative about veterans.”

Schmidt said Cadeau shows how veterans are returning to college and civilian life and making a difference in their communities. He said stereotypes pigeonhole and marginalize returning soldiers; Cadeau's show helps change that perception.

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Cronkite junior Christopher Cadeau (right) interviews blind Ironman participant and Army vet Michael Somsan (left) and his guide Dominic Bernardo for Cadeau's radio podcast "Veterans Diaries."

The broadcast runs from 4:30 to 5:30 p.m. each Wednesday during the semester. Cadeau said the premise of “Veterans Diaries” is about empowerment and overcoming obstacles.

“There are already a lot of sports shows on The Blaze, and I wanted to do something that had impact on the community," Cadeau said. "Stories one hears on the show can help other veterans, and civilians can see they aren’t broken and everyone has hiccups in their lives."

Cadeau said it took him a while to catch on before he hit his stride, and stopped a practice he employed in the beginning of the show.

“I’d conduct these pre-interviews with my guests, and they’d sit with me and tell me all these great things. And when we’d get on the air, it was crickets,” Cadeau said. “I discovered by knowing all the answers beforehand, I’d be leading them into questions I already knew the answer to, and it took my curiosity away. I don’t do that any longer.”

Army veteran and Purple Heart recipient Ian Parkinson, who was the first guest on the show and has been interviewed by international media, said Cadeau was an excellent host.

“The dialogue didn’t feel set up, and it was organic,” said Parkinson, a ASU graphic information technology major. “Chris isn’t afraid to ask questions because he can relate to me because of his military background. He has a passion for this show, and he made me feel I could be open about a lot of things.”

Around the sixth episode, Cadeau says he realized he wasn’t serving his entire audience. He had been ignoring angry vets who needed to vent.

“If I’m not highlighting the entire military demographic, then I’m not doing my job as a journalist,” Cadeau said. “Then I started bringing them on the air, and noticed some of the shows started taking off.”

By taking off, Cadeau means some of his most popular shows would receive 850 clicks and more than two dozen shares.

Cadeau has interviewed amputees, Vietnam vets, researchers, advocates, politicians and film directors. Their discussions range from head injuries to sexual harassment to post-traumatic stress disorder.

Cadeau said he tries “to keep people in their ‘whys.’”

“I don’t want to know what people do; I can do an Internet search and figure that out,” he said. “But when you talk about why they do what they do, everything starts to resonate.”

Sweatt was on “Veterans Diaries” for a two-part episode and called the show cathartic.

“His show serves to tell stories about the military experience, the transition road and individuals’ victories in the face of adversity,” said Sweatt, COO for the Veterans Directory.

For the upcoming semester, Cadeau is preparing for at least a dozen shows, including a Pat Tillman tribute with friends, teammates and other associates.

“The show is good now, but I’m really looking forward to where it will be in a year,” Schmidt said.  

“Veterans Diaries” will air again Jan. 11 on Blaze Radio, which can be heard on 1330 AM or on the website. Previous episodes are available on the "Veterans Diaries" SoundCloud page.