Answer: Feed it coffee or caffeine. In fact, coffee seems to be better.
Caffeine and coffee as therapeutics against Alzheimer’s disease.
Abstract
Epidemiologic studies have increasingly suggested that caffeine/coffee could be an effective therapeutic against Alzheimer’s disease (AD). We have utilized a transgenic mouse model for AD in well-controlled studies to determine if caffeine and/or coffee have beneficial actions to protect against or reverse AD-like cognitive impairment and AD pathology. AD mice given caffeine in their drinking water from young adulthood into older age showed protection against memory impairment and lower brain levels of the abnormal protein (amyloid-beta; Abeta) thought to be central to AD pathogenesis. Moreover, “aged” cognitively-impaired AD mice exhibited memory restoration and lower brain Abeta levels following only 1-2 months of caffeine treatment. We believe that the cognitive benefits of chronic caffeine administration in AD mice are due to caffeine itself, and not metabolites of caffeine; this, because our long-term administration of theophylline to AD mice provided no cognitive benefits. In acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Abeta levels – similarly rapid alterations in plasma Abeta levels were seen in humans following acute caffeine administration. “Caffeinated” coffee provided to AD mice also quickly decreased plasma Abeta levels, but not “decaffeinated” coffee, suggesting that caffeine is critical to decreasing blood Abeta levels. Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of Abeta production through suppression of both beta- and gamma-secretase levels. These results indicate a surprising ability of moderate caffeine intake (the human equivalent of 500 mg caffeine or 5 cups of coffee per day) to protect against or treat AD in a mouse model for the disease and a therapeutic potential for caffeine against AD in humans.
Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice.
Abstract
Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer’s disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine’s established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.
