An unknown ingredient in coffee teams up with caffeine to stimulate blood levels of a critical protein called GCSF, short for granulocyte-colony stimulating factor, that appears to put off the development of Alzheimer’s disease. These were the conclusions of a team from the University of South Florida (USF), whose members conducted their research on mice and describe the work in a paper available in an early online issue of the Journal of Alzheimer’s Disease (JAD) this week.

Co-lead author Dr. Chuanhai Cao, a neuroscientist at USF, told the press that:

“Caffeinated coffee provides a natural increase in blood GCSF levels.”

“The exact way that this occurs is not understood. There is a synergistic interaction between caffeine and some mystery component of coffee that provides this beneficial increase in blood GCSF levels,” said Cao.

Previous studies have suggested that high intakes of coffee and caffeine during mid-life and later may reduce the risk of Alzheimer’s disease; indeed an earlier study by the same team at USF, showed that long-term caffeine consumption protected mice prone to Alzheimer’s disease against cognitive impairment and markedly reduced blood and brain levels of beta-amyloid protein, which is thought to cause the disease.

Because coffee contains many ingredients as well as caffeine, the researchers wondered if any of these also provide benefits against Alzheimer’s disease, and set out to compare the effect of caffeinated and decaffeinated coffee on cytokines in the bloodstream of mice with that of caffeine alone.

Cytokines are proteins that carry signals between cells and are known to play a critical role in the progression and development of Alzheimer’s.

They found that both in mice genetically engineered to be prone to Alzheimer’s and in their non-genetically engineered littermates, enhanced intake of caffeinated coffee “greatly and specifically” increased blood levels of three cytokines: GCSF, IL-10, and IL-6.

But, neither caffeine on its own (which resulted in high blood levels of caffeine), nor decaffeinated coffee had this effect, suggesting that another as yet unidentified ingredient in the coffee “synergized” or teamed up with the caffeine to “selectively elevate” these three cytokines in the mice’s bloodstream.

The researchers focused on GCSF because after a long period of coffee consumption, Alzheimer’s-susceptible mice showed improved performance in working memory, and GCSF was the only cytokine to show higher levels in the bloodstream over the same period.

Also, in previous research, they had reported that long-term GCSF treatment of mice prone to develop Alzheimer’s improved their cognitive performance via three mechanisms that could be complementary to the way caffeine suppresses production of beta-amyloid protein.

The three mechanisms that GCSF employs are: “recruitment of microglia” where it brings stem cells from bone marrow to enter the brain and mop up the amyloid beta protein; “synaptogenesis” where it creates new connections between brain cells; and “neurogenesis”, where it increases the birth of new brain cells or neurons in the brain.

“All three mechanisms could complement caffeine’s ability to suppress beta amyloid production in the brain,” said Cao.

Bringing all these results together, the researchers concluded that “coffee may be the best source of caffeine to protect against AD [Alzheimer’s Disease] because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD”.

Cao commented that:

“Together these actions appear to give coffee an amazing potential to protect against Alzheimer’s — but only if you drink moderate amounts of caffeinated coffee.”

GCSF is greatly reduced in people with Alzheimer’s. Investigators are in the throes of evaluating a USF clinical trial that tested how effective GCSF treatment could be in preventing full-blown Alzheimer’s in patients with mild cognitive impairment, a condition that precedes it.

The team hope to find the mystery coffee ingredient so that it can be used to enrich coffee and other drinks to provide long-term protection against Alzheimer’s.

TBecause they used “drip” coffee in the study, they can’t say if instant coffee would have the same effects.

Although this study was conducted in mice, the researchers said in a statement that they are currently doing clinical tests that suggest coffee and caffeine have similar protective effects in humans and hope to publish the findings soon.

The average American drinks between 1.5 and 2 cups of coffee a day, considerably less than the 4 or 5 daily cups that studies suggest may be necessary to protect against Alzheimer’s.

The researchers said they believe the best age to start moderate daily consumption of coffee to protect against Alzheimer’s is around 30 to 50, although studies suggest starting later than this also appears to give protection.

“We are not saying that daily moderate coffee consumption will completely protect people from getting Alzheimer’s disease,” said Cao, addinng that:

“However, we do believe that moderate coffee consumption can appreciably reduce your risk of this dreaded disease or delay its onset.”

Cao also said that coffee has other ingredients that may protect against Alzheimer’s:

“Coffee is high in anti-inflammatory compounds that also may provide protective benefits against Alzheimer’s disease.”

Apart from coffee, physical and mental activity also appear to reduce the risk of dementia, said the researchers.

Funds from the NIH-designated Florida Alzheimer’s Disease Research Center and the State of Florida paid for the study.

“Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer’s Mice.”

Chuanhai Cao, Li Wang, Xiaoyang Lin, Malgorzata Mamcarz, Chi Zhang, Ge Bai, Jasson Nong, Sam Sussman, Gary Arendash.

JAD, Vol 25, No 2, IN PRESS Abstract published online 28 June 2011.

Additional source: University of South Florida (USF Health).

Written by: Catharine Paddock, PhD