Caffeine in Treatment for Alzheimer's Disease
The cause for most Alzheimer's cases is still mostly unknown except for 1% to 5% of cases where genetic differences have been identified. Several competing hypotheses other than genetics exist trying to explain the cause of the disease:
a. Cholinergic hypothesis: It proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.
b. Amyloid hypothesis: Amyloid precursor protein (APP) is a protein found widely throughout the body. A fault with the processing of amyloid precursor protein (APP) in the brain leads to the production of a short fragment of APP known as beta-amyloid (ßA). The theory rests on the idea that it is the accumulation of this sticky protein fragment (amyloid plaques) in the brain that triggers the disruption and destruction of nerve cells that causes Alzheimer's disease.
c. Tau hypothesis: In normal cells, tau stabilizes axonal microtubules, which are the tracks for intracellular traffic. In AD, tau becomes abnormally phosphorylated, aggregates into paired helical filaments and loses its ability to maintain the microtubule tracks.This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.
Hypothesis b and c are favorite among the researchers and drug designers alike. A combination of both amyloid and tau too is being considered as the possible reason to Alzheimer disease. As we lack a complete and true understanding of the causes, the clinical trials of drugs designed for AD never end with a positive hope.
A review published in Journal of Caffeine Research, aims to identify the hypothesized role of caffeine in reducing ßA levels and its link with AD.
Caffeine
Some salient discoveries reported in the review are:
1. Caffeine's hydrophobic nature allows for the rapid absorption through all biological membranes and it can easily cross the blood-brain barrier.
2. Research has demonstrated that caffeine intake may protect against AD, and may also lead to remission of symptoms for those who are already affected.
3. Studies in mice shows that coffee was effective in slowing down or prevent the development of ßA plaques.
4. Alertness and response increases as mild to moderate caffeine is ingested, suggesting a possible role of caffeine in the inactive AD patients.
5. Results from epidemiological studies have also reported that coffee and/or caffeine consumption may reduce AD risk.
6. In a study involving the caffeinated mice category, cerebrum had nearly a 50% reduction in levels of ßA, which is known to accumulate into plaques—the hallmark hypothesis of the cause of AD.
7. Caffeine reverses cognitive impairment and decreases brain ßA levels in aged AD mice.
However these studies have a few catch to them. Firstly, the experiment's are all on mices, no human subject or trial is reported. Secondly, the intake of coffee, provides many other chemicals including caffeine, so the results can be debated. Moreover, the dosage too has to be determined because excess of caffeine comes with its own problems.
Lastly, a genetic study focusing on ßA toxicity in a transgenic Caenorhabditis elegans AD model revealed that the primary protective component is likely not caffeine, although caffeine alone can show moderate protection.
Article citation: Mohan, A.; et. al. Caffeine as Treatment for Alzheimer's Disease: A Review. Journal of Caffeine Research 2015. DOI:10.1089/jcr.2014.0027. (text and citation therein)
