In France, 900,000 people suffer from Alzheimer’s disease or another related disease. The risk of developing Alzheimer’s disease depends on genetic and environmental factors. Among the latter, various epidemiological studies suggest that regular and moderate consumption of caffeine slows down cognitive decline linked to aging and the risk of developing Alzheimer’s disease. In a new study published in the journal Braina team from Inserm, the Lille University Hospital and the University of Lille, within the Lille Neuroscience and Cognition research center, have taken a further step in understanding the mechanisms underlying the development of Alzheimer’s disease.
They have just highlighted that the increase pathologicalpathological of certain receptors in neurons at the time of disease development promotes the loss of synapsessynapsesand in fact, the early development of memory disorders in an animal model of the disease. Their results also confirm the interest in conducting clinical testsclinical tests to measure the effects of caffeine on the brainbrain of patients at an early stage of pathologypathology.
In the beginning, the slow degeneration of neurons
Alzheimer’s disease is characterized by disorders of memory, executive functions and orientation in time and space. It results from a slow degeneration of neurons, beginning at the level of theseahorseseahorse (a brain structure essential for memory) and then spreading to the rest of the brain. Patients with this pathology have two types of microscopic lesions in their brain: senile plaques (or amyloid plaques)) and neurofibrillary degeneration (or Tau pathology), contributing to the dysfunction of neurons and their disappearance.
Studies have already shown that the expression of certain receptors, called A2A, were found increased in the brains of patients with Alzheimer’s disease in the hippocampus. However, the impact of the deregulation of these receptors on the development of the disease and associated cognitive disorders remained unknown until now. In a new study, a research team led by Inserm researcher David Blum looked into this question.
Brain abnormality: deregulated expression of A2A receptors
Scientists have managed to reproduce an early increase(3) in the expression of adenosinergic A2A receptors, as observed in the brains of patients, in a mouse modelmouse model of Alzheimer’s disease which develops amyloid plaquesamyloid plaquesThe aim was to assess the consequences of this increase on the disease and to describe the mechanisms involved.
The results of their research show that the increase in A2A receptors promotes the loss of synapses(4) in the hippocampus of “Alzheimer’s mice”. This has the effect of triggering memory disorders early in the animals. The scientists then showed that a dysfunction of certain brain cells, the microglial cellsmicroglial cellspartly responsible for theinflammationinflammation brain observed in the disease, could be involved in the loss of synapses, in response to an increase in A2A receptors.
Similar mechanisms had already been previously described by the team, this time in another model of the disease developing Tau lesions(5).
” These results suggest that increased expression of A2A receptors alters the relationship between neurons and microglial cells. This alteration could be at the origin of an escalation of effects leading to the development of the observed memory disorders. “, explains Émilie Faivre, co-author of the study, researcher at the Lille Neuroscience and Cognition research center (Inserm/University of Lille/CHU of Lille).
Several studies have already suggested that regular, moderate caffeine consumption (corresponding to consuming 2 to 4 cups of coffee per day) could slow cognitive decline linked to aging and the risk of developing Alzheimer’s disease.
In 2016, the same research team described one of the mechanisms by which caffeine could have this beneficial effect in animals, reducing cognitive disorders associated with Alzheimer’s disease. The scientists then showed that the effects of caffeine were linked to its ability to block the activity of A2A adenosinergic receptors, the same receptors whose expression is abnormally increased in the brains of people with Alzheimer’s disease(6).
Coffee, an ally to protect against Alzheimer’s disease? Thibaud Lebouvier, neurologist, and David Blum, researcher, explain how coffee proves to be protective against the development of Alzheimer’s-related diseases. They present their CAFCA research project currently in the process of including patients. © CHU Lille
” By describing, in our new study, the mechanism by which the pathological increase in the expression of A2A receptors causes a cascade of effects leading to a worsening of memory disorders, we confirm the interest of therapeutic avenues that could act on this target. We therefore once again highlight the interest of testing caffeine in the context of a clinical trial on patients with early forms of the disease. Indeed, we can imagine that by blocking these A2A receptors, the activity of which is increased in the patient, this moleculemolecule can prevent the development of memory disorders and other symptomssymptoms cognitive and behavioral “, continues David Blum, research director at Inserm, co-last author of the study.
A phase 3 clinical trial, called CAFCA, led by the Lille University Hospital, is currently underway. Its objective is to evaluate the effect of caffeine on the cognitive functions of patients with early to moderate forms of Alzheimer’s disease.
