SMHS neuroscientist Jonathan Geiger, PhD, one of the study’s authors and the originator of this caffeine research project, says this barrier protects the central nervous system from the rest of the body's circulation, providing the brain with its own regulated microenvironment.

Previous studies have shown that high levels of cholesterol break down the BBB which can then no longer protect the central nervous system from the damage caused by blood borne contamination. BBB leakage occurs in a variety of neurological disorders such as Alzheimer's disease, Geiger notes.

In this study, SMHS researchers gave rabbits 3 mg caffeine each day – the equivalent of a daily cup of coffee for an average-sized person. The rabbits were fed a cholesterol-enriched diet during this time. After 12 weeks a number of laboratory tests showed that the BBB was significantly more intact in rabbits receiving a daily dose of caffeine.

“Caffeine appears to block several of the disruptive effects of cholesterol that make the blood-brain barrier leaky,” says Geiger. “High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier. For the first time we have shown that chronic ingestion of caffeine protects the BBB from cholesterol-induced leakage.”

Caffeine appears to protect BBB breakdown by maintaining the expression levels of tight junction proteins. These proteins bind the cells of the BBB tightly to each other to stop unwanted molecules crossing into the central nervous system.

The findings confirm and extend results from other studies showing that caffeine intake protects against memory loss in aging and in Alzheimer’s disease.

“Caffeine is a safe and readily available drug and its ability to stabilise the blood-brain barrier means it could have an important part to play in therapies against neurological disorders,” says Geiger.

The caffeine study at SMHS parallels work by another researcher on Geiger’s team, Othman Ghribi, who is researching the roleof diet and the environment in Alzheimer’s disease. This research is the focus of new funding from the National Institutes of Health (NIH) for a biomedical research scientist at the University of North Dakota (UND) School of Medicine and Health Sciences.

Ghribi has received a prestigious five-year RO1 grant, totaling nearly $1.5 million, from the National Institute of Environmental Health Sciences to study the links between high cholesterol levels and Alzheimer’s disease. This is the largest individual grant awarded to a UND researcher for the study of Alzheimer’s disease (AD). RO1 grants are very difficult to obtain and are awarded to relatively few researchers.

Investigations to-date in Ghribi’s lab have suggested that high cholesterol levels in the blood may be a risk factor for developing Alzheimer’s disease, Ghribi says.

In addition to cholesterol, trace metals such as iron have also been suspected to play a role in the “sporadic” forms of AD, by far the most prevalent form of the disease. A much smaller proportion of AD cases are related to a genetic mutation, he says. “In the absence of known genetic factors that lead to the sporadic form of the disease, any knowledge about risk factors that can cause or exacerbate the disease would allow us to better understand the pathophysiology of this disease,” says Ghribi, assistant professor of pharmacology, physiology and therapeutics. It’s been shown that people with high cholesterol as well as high levels of iron in the brain are more susceptible to have the disease than people who have either high cholesterol or high levels of iron in the brain, Ghribi says.

However, to date, “there’s been no animal model that combines these two risk factors to help us understand the progression of AD,” he says. It’s the combination of the risk factors, high levels of cholesterol and iron, that interests him most. He has developed an animal model that exhibits both increased cholesterol and iron levels to test his hypothesis.

“It is estimated that about five million U.S. citizens have Alzheimer’s disease,” Ghribi says. “If we don’t find some answer about its cause or the mechanisms that lead to the disease, that number will increase to 15 million people by 2050. That’s a huge health, economic and emotional burden for the people living with Alzheimer’s, the families of these people, and the government.”

Ghribi expects that, by the end of his study, “I will have a better understanding of some of the factors that lead to Alzheimer’s disease,” he says, and “if we find that the metabolism of cholesterol and/or iron is a risk factor of Alzheimer’s disease, then regulation of the metabolism of these molecules may prevent or stop the progression of Alzheimer’s disease.”

The NIH grant will support the hiring of three or four employees to work in his laboratory, he notes. Ghribi’s investigations were initially funded by North Dakota Biomedical Research Infrastructure Network (BRIN), now called the North Dakota IDeA Network of Biomedical Research Excellence (INBRE).

More recently, his studies have been funded by the Center of Biomedical Research Excellence (COBRE), a highly competitive federal initiative that helps support researchers in states which traditionally have not attracted large amounts of NIH research funding.