Caffeine Blocks, Reverses Alzheimer’s Symptoms in Mice

by Aalok Mehta

August 27, 2009

If you don’t drink coffee every day, now may be a good time to grab a cup—or five. Large doses of caffeine can not only prevent memory impairment and other symptoms of Alzheimer’s disease in mice, they can also reverse damage that has already occurred, according to a pair of new studies.

Though the findings have serious caveats—they come from a mouse model of the symptoms of Alzheimer’s disease and involve caffeine amounts that far exceed what’s found in the average person’s diet—the results are encouraging enough that the researchers have jump-started human clinical trials.

“Within two or three hours of a single administration of caffeine in mice, both brain and blood levels of the bad beta-amyloid protein [the main component of the plaques that characterize Alzheimer’s disease] are reduced appreciably,” says lead author Gary Arendash, a biology professor at the University of South Florida. “So caffeine may not work just to reduce risk but as a treatment as well.”

Five cups of coffee

A report by European researchers that found that people diagnosed with Alzheimer’s disease tended to consume less caffeine than average inspired his investigation, Arendash says, as did several smaller studies supporting that finding. But because such epidemiological surveys are complex and difficult, and so can be unreliable, it “was all the more reason to do a highly controlled study in Alzheimer’s disease mice where we control for everything and leave as the only variable coffee intake,” he says.

In the new studies, which appear in the July issue of Journal of Alzheimer’s Disease, Arendash and his colleagues worked with about 50 mice. About half received 1.5 mg of caffeine in their drinking water a day at various stages of development. That translates to a dose of about 500 mg a day for humans—the amount of caffeine in five regular cups of coffee or 14 cups of tea.

Because some prior work had shown little effect in people imbibing about 150 mg of caffeine a day—the average daily intake among adults in the United States—the mouse dose was chosen carefully to be at the upper end of what is considered moderate caffeine consumption in humans, Arendash says.

After two months, the mice drinking plain water continued to show characteristic declines in thinking and memory, but the caffeine-drinking mice performed about as well as healthy mice with no trace of dementia. The caffeinated mice also showed half as much buildup of beta-amyloid protein as their counterparts.

In addition, the scientists found that a single dose of caffeine could cause significant decreases in beta-amyloid in both the brains and blood of the mice. The team has recently observed similar changes in a group of human patients, “which indicates that the mice might be an effective index of what might be going on in humans,” Arendash says.

Regular caffeine consumption did not improve memory in normal mice, Arendash adds, suggesting that caffeine is working specifically against Alzheimer’s. In previous work, they found that caffeine might do this by blocking inflammatory processes, dropping the levels of two enzymes directly involved in the manufacture of amyloid beta, but how it might do this remains hazy.

Caffeine highs

The evidence for caffeine’s neuroprotective effects is mixed, says Kamal Masaki, a professor of geriatric medicine at the University of Hawaii, Manoa, who was not involved in the new research. Several studies, including one she worked on in 2000 that found that caffeine helps shield against Parkinson’s disease, did not find any such associations for Alzheimer’s. However, the caffeine levels used in these studies were much lower than 500 mg, in part because so few people even in large studies consumed that much of the stimulant, she says.

But the new work is a “very well done mice study,” she says, and does a good job of making a case for caffeine’s potential in Alzheimer’s. Because caffeine has been used for thousands of years, is well tolerated and gets into the brain very quickly, “it’s definitely worth a try to see if they can replicate some of these findings in humans,” she says.

Arendash doesn’t know if doses less than 500 mg would have a similar effect. “It could be less, but I suspect it’s not going to be much less than that,” he says, pointing out that even when taken at those levels, while higher than the general comfort level for many people, the stimulant poses almost no health risks except to a select group, including those who are pregnant or have blood pressure issues.

Caffeine’s long history, ready availability and safety justify the attention it garners over other compounds that also have potential helpful effects against Alzheimer’s, Arendash says. Because it is so well known, for instance, he has already begun Phase II clinical trials, skipping the stage at which scientists primarily assess safety and dosing.

“Many scientists think that the only thing that can benefit Alzheimer’s disease is a synthetic drug,” which would take many more years to develop, he says. “I hope not.”