Caffeine and Coffee as Therapeutics Against Alzheimer's Disease

Abstract

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-β; Aβ) thought to be central to AD pathogenesis. Moreover, "aged" cognitively-impaired AD mice exhibited memory restoration and lower brain Aβ 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 Aβ levels -similarly rapid alterations in plasma Aβ levels were seen in humans following acute caffeine administration. "Caffeinated" coffee provided to AD mice also quickly decreased plasma Aβ levels, but not "decaffeinated" coffee, suggesting that caffeine is critical to decreasing blood Aβ levels. Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of Aβ production through suppression of both β-and γ-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.

Coffee, but not caffeine, has positive effects on cognition and psychomotor behavior in aging

“…We chose not to use decaffeinated coffee for these studies because it contains 60 % less chlorogenic acids and 70 % less chlorogenic acid lactones than caffeinated coffee (Chu et al 2009). In addition, in contrast to the results seen with caffeine and caffeinated coffee, decaffeinated coffee was previously unable to decrease plasma amyloid-beta when provided to AD mice (Arendash and Cao 2010).…”

“…Furthermore, the overall contribution of individual components of coffee to the health benefits of coffee consumption has not been explored. In a series of studies using AD transgenic mice, Arendash and colleagues found that caffeine can protect against, and even reverse, memory loss and AD pathology (Arendash and Cao 2010). In addition, caffeine and/or caffeinated coffee (but not decaffeinated coffee) affected plasma levels of amyloid-beta in mice and humans with AD (Arendash et al 2006;Cao et al 2009).…”

“…In addition, caffeine and/or caffeinated coffee (but not decaffeinated coffee) affected plasma levels of amyloid-beta in mice and humans with AD (Arendash et al 2006;Cao et al 2009). They concluded that clinical trials are warranted to test the use of caffeine and caffeinated coffee as safe, inexpensive, and effective therapeutics against AD (Arendash and Cao 2010). In another study, four coffees with varying degrees of caffeine and pyroglutamate, an amino acid found in coffee known for its cognitive enhancing activities, were assessed for their effects on learning in mice (Maeso et al 2006).…”

Machado-Joseph Disease / Spinocerebellar Ataxia Type 3

“…Studies in mouse models of Alzheimer's and Parkinson's diseases found that caffeine could alleviate pathological signs and behavior deficits in these neurodegenerative disease paradigms, by antagonizing A2A adenosine receptors (Arendash and Cao, 2010;Prediger, 2010;reviewed in Cunha and Agostinho, 2010). Moreover, administration of caffeine and other stimulants in orexin/ataxin-3 transgenic narcoleptic mice induced an increase in motor activity but the effects on neuropathology remain to be investigated (Okuro et al, 2010) and should be further investigated in MJD models.…”

Polyphenol Ellagic Acid-Targeting To Brain: A Hidden Treasure

“…These drugs have included acetylcholine precursors, muscarinic agonists, nicotinic agonists, andacetylcholinesterase inhibitors [9] . Herbal drugs are alsopre-clinically as well as clinically tested and shown to be very effective as Galantamine [19,20] , Ginkgo biloba [21,22] , Bacopa monnieri (brahmi) [23,24] , Celastrus paniculatus [25,26] , Curcumin [27][28][29] , coffee [30][31][32] and Lavender essential oil [33] . Many naturally occurring compounds have been proposed as potential therapies to slow or prevent the progression of AD, mostly by acting as antioxidants [34] , but also with some direct anti-amyloid actions [35] .…”