Alzheimer’s disease is a neurodegenerative disease characterized by impaired memory and other cognitive / behavioural deficits: aggression, aphasia (language disorder), agnosia (confusion of the recognition of the environment), apraxia (clumsy gesture).
If the diagnosis of the probability of Alzheimer’s disease is based on various clinical criteria aided by the determination of biomarkers in cerebrospinal fluid, or even MRI or metabolic imaging, the diagnosis of certainty is based on the neuropathological observation of extraneuronal plaques consisting of amyloid peptides (normally formed small proteins that accumulate toxicly outside neurons) and intraneuronal lesions composed of abnormal Tau proteins (proteins that normally promote cellular communication within the neuron). These lesions cause dysfunction of neuronal cells, causing cognitive disorders.
Caffeine and Alzeihmer
Coffee consumption has a particular impact on this risk. Coffee is the most consumed drink in the world after water. Coffee is also the main source of caffeine, which remains to this day its best-known constituent .
Caffeine is the most consumed psychoactive substance in the world. It is well established that it promotes attentional processes, awakening, information processing and therefore has a significant impact on cognitive performance in humans and animals.
Recent work also suggests an effect of caffeine on memory processes, and long-term memory in particular, independent of its attentional effects. This observation is linked to different epidemiological studies suggesting that habitual consumption of caffeine reduces cognitive decline during aging.
Other prospective studies also focus on the inverse relationship between caffeine consumption and the risk of developing Alzheimer’s disease. The protective effects of caffeine would be optimal for doses of 3 to 4 cups a day.
Interestingly, various experimental studies on animal models of Alzheimer’s disease reproducing lesions and associated memory disorders demonstrate a beneficial effect of caffeine at comparable doses, even if the effects on the behavioural symptoms of the disease have recently been discussed .
What are the mechanisms of action of caffeine in the brain?
The main targets of caffeine are receptors called adenosinergic receptors. The effects of caffeine are particularly related to its ability to block one of these receptors called adenosinergic A2A receptor.
A few years ago, our team demonstrated that specifically blocking this receptor through genetic approaches and a chemical derivative of caffeine reduced memory disorders, neural communication disorders, and Tau protein dysfunctions in one model animal of Alzheimer’s disease.
In a new study, our team, in collaboration with colleagues from the University of Lisbon and Bonn, has just demonstrated that blocking A2A adenosinergic receptors by this same caffeine-derived compound reduces amyloid lesions in the cortex and associated memory disorders in an animal model reproducing amyloid plaques.
This new study therefore suggests that caffeine-derived compounds targeting A2A adenosinergic receptors act positively towards the two brain lesions characteristic of the disease.
Towards a therapeutic track in humans?
All these observations suggest that the use of molecules derived from caffeine would be a therapeutic option in patients with Alzheimer’s disease. It is very interesting to note that this type of molecule exists and has already been the subject of clinical trials in the context of Parkinson ‘s disease. It is therefore possible and interesting to reposition these molecules in the therapeutic context of Alzheimer’s disease.
Before considering studies in humans, we need to provide additional convergent elements reinforcing the concept that it is important to block A2A receptors. These are the experimental studies that we are currently conducting. We hope to be able to define a clinical trial strategy in the next 3 to 5 years and raise funds for this purpose.