Caffeine May Protect Blood-Brain Barrier from Cholesterol Damage

GRAND FORKS, N.D., April 4 -- A daily dose of caffeine broke the link between hypercholesterolemia and Alzheimer's disease in a rabbit model.
After 12 weeks on a high-fat diet, animals given the equivalent of a single cup of coffee a day had a more intact blood-brain barrier compared with animals that did not receive caffeine, Jonathan D. Geiger, Ph.D., of the University of North Dakota, and colleagues, reported in the April issue of the Journal of Neuroinflammation.
"High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier," said Dr. Geiger. "For the first time we have shown that chronic ingestion of caffeine protects the blood-brain barrier from cholesterol-induced leakage."
A spokesperson for the Alzheimer's Association said the relationship between hypercholesterolemia and Alzheimer's disease remains unclear, as is the contribution of a leaky blood-brain barrier to the disease process.
Sam Gandy, M.D., Ph.D., chair of the National Medical and Scientific Advisory Council for the association and an Alzheimer's researcher at Mount Sinai School of Medicine in New York, also noted that the preclinical model used in the study has not been validated in Alzheimer's disease.
Epidemiologic and experimental studies have suggested that chronic administration of caffeine has beneficial effects for a number of neurovascular disorders, including Alzheimers' disease.
To test their theory that caffeine might counter cholesterol's disruption of the blood-brain barrier, the researchers compared the effects of chronic caffeine administration in rabbits fed a cholesterol-enriched diet or a standard diet.
The daily caffeine dose was 3 mg, administered in the animals' drinking water.
After 12 weeks, the authors examined the animals' olfactory bulbs for evidence of blood-brain barrier leakage and tight junction protein expression levels, activation of astrocytes, and microglia density.
They chose the olfactory bulb because of its intact blood-brain barrier and because olfactory dysfunction is common in Alzheimer's patients and may be one of the earliest signs of the disease.
Blood-brain barrier leakage was assessed by changes in the immunoreactivity of IgG and fibrinogen.
The cholesterol-enriched diet markedly increased IgG and fibrinogen extravasation. Daily caffeine administration blocked that extravasation.
In contrast, caffeine had no effect on IgG and fibrinogen extravasation in animals fed the control diet.
"Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the blood-brain barrier, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease," the authors concluded.
Acknowledging that a leaky blood-brain barrier "is probably not a good thing," Dr. Gandy said the study's relevance to clinical Alzheimer's is unclear.
"These are interesting animal data that merit extension to humans to determine relevance," he said. "Any relationship between cholesterol, blood-brain barrier, and Alzheimer's at this point remains intriguing but speculative."
Dr. Geiger and co-authors reported no disclosures.
Additional source: Journal of NeuroinflammationSource reference: Chen X, et al "Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease" J Neuroinflammation 2008; 5: 12.