'Alzheimer's Gene' Protects Children From Severe Diarrhea

"In earlier studies, we found that shantytown children in Northeast Brazil who suffer from early childhood diarrhea and malnutrition suffered from lasting physical and cognitive consequences. However, some children who have the same diarrhea and malnutrition are protected from the developmental problems if they have the "Alzheimer's gene" (APOE4)," says Dr. Richard Guerrant, founder and director of the Center for Global Health at the University of Virginia School of Medicine. "Basically, we believe this gene protects the children early in life by helping them survive severe malnutrition, but the same gene potentially contributes to a multitude of problems later in life."

Guerrant and colleagues at Federal University of Ceará recently received a $1.3 million grant from the National Institute of Child and Human Development to study the striking link. Guerrant and Dr. Aldo A. M. Lima, professor and director of the Clinical Research Unit & Institute of Biomedicine at Federal University of Ceará have a 25-year collaboration addressing children's health and development issues. Dr. Lima and Dr. Reinaldo Oriá are working as the principal investigators in Brazil.

Severe diarrhea and its accompanying malnutrition kill more than 3 million people worldwide each year and developmentally impair many millions more children who survive repeated bouts of diarrhea, while Alzheimer's afflicts more than 20 million people worldwide each year.

"This might have important implications for Brazil and other developing countries, where diabetes and cardiovascular disease are also becoming critical issues in public health," says Oriá, an associate professor at Federal University of Ceará and a former research fellow at the University of Virginia. Oria says the primary goal of the study will be to develop interventional therapies based on critical nutrients which children need for their cognitive and physical development.

In studies in mice at UVa, these researchers have shown that those mice who do not have the APOE4 gene suffer far worse malnutrition when they are weaned early. Oria says they are looking to see if arginine, an amino acid, can help lessen the devastating consequences of severe diarrhea and malnutrition.

In addition, Guerrant says the research will also shed further light on situations where negative genetic traits are found to have beneficial effects that likely help to explain their presence in human evolution. An example of this phenomenon, called a balanced polymorphism, is sickle cell anemia, a genetic disease in which a double "dose" of the sickle cell gene causes red blood cells to form odd shapes and results in pain and anemia. A single "dose" of the same gene, however, makes a person resistant to malaria, a deadly tropical disease.

Oria adds that if the APOE4 gene indeed proves to be a balanced polymorphism, this could greatly help us understand and reduce the long-term impact of diarrhea and malnutrition. He says the genetic imprint early in life due to the "switch-on" of genes to sustain body mass, may have lasting consequences later in life. This genetic "switch" could elucidate ways to "turn-on" the protection when they are most vulnerable and then "turn-off" the genetic switch which helped them in their youth, but will cause them more problems as they age.

"We are very excited about this ongoing research with the promise of hope and better health it offers to millions of children silently suffering the devastating consequences of diarrhea and malnutrition worldwide," Guerrant says.