Updated: September 2020
With 225,000 new cases diagnosed each year in France, Alzheimer's disease continues to take a devastating toll. Worse still, it is estimated that one in two cases goes undiagnosed due to a lack of precise knowledge about this neurodegenerative disease. At the Pasteur Institute in Lille, new approaches are being implemented to better understand the mechanisms of the disease and try to curb this scourge.
The aging population is leading to an increase in the number of people affected by neurodegenerative diseases such as Alzheimer's (5% of those over 65 and 15% of those over 85) and Parkinson's. People with dementia require significant support from family members or specialized organizations. Currently, 3 million people in France are directly or indirectly affected by this disease.
Complementary strategies for understanding the disease
La Alzheimer's disease is characterized by neuronal loss. and synaptic damage in specific areas of the brain, causing memory and behavioral problems, as well as a deterioration in the living conditions of patients.
Given this situation, it is essential to better understand the mechanisms behind the development of these cognitive disorders. Understanding a disease that evolves over time is a highly complex undertaking, requiring numerous long-term studies and substantial resources. This is a crucial step for the future, in order to better anticipate, diagnose, and ultimately treat this brain disease. The mission is not simple, but the Pasteur Institute of Lille has equipped itself with the best resources. Dr. Jean-Charles Lambert's team, among the leaders in genetics for Alzheimer's disease, is responsible for discovering 75% of the genetic determinants of this neurodegenerative disease.
Dr. Jean-Charles Lambert, surrounded by Devrim Kilinc and Marcos Costa: three researchers at the head of two new research techniques.
However, to date, it remains extremely difficult to link these responsible genes to structural and functional alterations in the brain's neural networks. This is why it is crucial to develop tools that can establish a link between cellular alterations and overall network dysfunction.
Two research areas to study the mechanisms
"Our proposal aims to develop complementary strategies for studying the cellular and molecular mechanisms of Alzheimer's disease. Combined with ongoing research, we believe these new approaches are essential to accelerating progress in research on Alzheimer's disease and other age-related illnesses." explains Dr. Marcos Costa, neuroscientist in charge of the organoid research project, a miniature imitation of the human brain.
Discovery of new genetic data
A second project led by Doctors Kilinc and Lambert aims to identify the role of synapses, that is, the connections between two neurons, in the Cognitive decline symptomatic of Alzheimer's disease. To achieve this, researchers recreate diseased neural networks in vitro. This tool, called microfluidics, models the complexity of the human brain at the micrometric scale by reproducing neural circuits.
At the scale of a single drop, these complex analyses make it possible to study how these mechanisms depend on genetic risk factors and neuroinflammatory factors.
Microfluidics: Modeling neural circuits
Thanks to this technology, researchers were able to observe that a significant number of genes associated with the risk of developing Alzheimer's disease did, in fact, have a synaptic function. Certain brain lesions revealed the aggregation of a protein, amyloid-β, responsible for neuronal death.
"This innovative approach could lead to new therapeutic avenues for improving neuronal transmission and preventing cognitive decline." "In short," summarizes Dr. Jean Charles Lambert, "the study of Alzheimer's disease requires patience more than ever. These new approaches, which are long-term in nature, are promising and offer the prospect of developing new treatments for this scourge."
A “mini-brain” to better understand disorders
Developing a new brain organoid model a million times smaller than a human brain is the new challenge undertaken by researchers at the Pasteur Institute in Lille. By culturing them in a way that mimics the environment of brain development, stem cells differentiate and organize themselves into a structure resembling the developing brain.
The organoid, more commonly known as the “mini-brain”, constitutes a three-dimensional cell culture system that can serve as living material to mimic disease and evaluate the effectiveness of new treatments.
“Once we understand how the disease changes neurons, we can begin transforming blood cells taken from Alzheimer's patients into neurons to study the specific alterations in each individual. We hope this will be possible within 5 to 10 years,” explains Dr. Costa. This process, as lengthy as the disease itself takes to develop in the human brain, is costly research, made possible by the ongoing support of the foundation's donors.
A researcher's journey
Devrim Kilinc: Research into the Infinitesimally Small
As a research scientist in the Alzheimer's unit, Dr. Kilinc works at the microscopic level to treat one of the greatest scourges of our time. A specialist in cell culture using microfluidics, he develops techniques at the microscopic scale. It's a profession that demands rigor and precision.
Originally from Turkey, Devrim Kilinc first studied mechanical engineering before going to the United States to pursue a doctorate, aiming to become a biomedical engineer in neuroscience. After a first post-doctoral position in Paris in 2008, followed by a second in Dublin, he returned to France in 2016 where he joined the team of Dr. Jean-Charles Lambert, specializing in Alzheimer's disease.
“I chose to join the Pasteur Institute of Lille because of the Foundation's reputation, but above all because of the mission entrusted to me within the laboratory. It is a real source of pride to be able to contribute my expertise and participate in discoveries about Alzheimer's disease.” he affirms, as ambitious research projects are being developed in the laboratory.
Microfluidics Specialist
Devrim's daily work involves developing cell culture models using microfluidics. This technology manipulates fluids on a water droplet scale. The goal of this device is to optimize neuronal culture and identify toxic molecules associated with Alzheimer's disease.
His research requires versatility, from laboratory experimentation to computer analysis phases, and numerous interactions with other experts on the team. “To sum up, I could say that I work on something very, very small.”His work is on the micrometer scale but should allow for major advances in this disease which affects nearly 900,000 people in France.
When he's not immersed in the microscopic world, Dr. Kilinc enjoys escaping to wide open spaces and indulging his passion for travel. A badminton player, he has successfully motivated his colleagues to play as a team, which is ideal for group cohesion—another essential quality in research.
Everything you need to know about Alzheimer's disease
In France, Alzheimer's disease is the fourth leading cause of death. More than 900,000 people are affected by this condition, and a new case is diagnosed every three minutes. To combat this scourge, risk factors such as age, a sedentary lifestyle, diabetes, high blood pressure, cardiovascular problems, and minor head injuries must not be overlooked.
Symptoms
Initially, Alzheimer's disease most often manifests as memory problems. Subsequently, other brain functions are affected, with the progression varying considerably from one patient to another. Gradually, as the disease progresses, everyday tasks become difficult to perform and adapting to new situations becomes particularly challenging.
- Memory problems (amnesia): This is often the first complaint. Initially, the person has difficulty retaining new information. They often ask for repetition, repeating the same actions several times. Then, as the disease progresses, older memories gradually fade.
- Inability to recognize and name objects, familiar people, or even sounds (agnosia): Patients experience daily discomfort that can vary in severity from case to case.
- Difficulties in performing movements (apraxia): The patient has difficulty performing everyday tasks that were previously automatic, such as using a fork or a toothbrush, despite having intact motor functions. These difficulties contribute significantly to the loss of independence.
- Language (aphasia) and numerical disorders: Verbal communication can quickly become problematic.
- Disorientation in time and space: The patient loses their sense of time and may become disoriented in a familiar environment. This highly anxiety-provoking disorder leads to wandering or aimless pacing.
- Sleeping troubles : They worsen as the disease progresses, but can also be early signs. Sleep becomes lighter, nighttime insomnia becomes frequent, and the duration of daytime sleep increases.
- Mood disorders : Anxiety, irritability, apathy, depression. Experts estimate that 60% of Alzheimer's patients are affected by apathy, which is common from the onset of the disease. It manifests as a persistent lack of motivation, a loss of initiative, disinterest in one's surroundings, and a decline in social activities.
- Depression is different from apathy. Its specific signs are persistent sad mood, pessimistic rumination, feelings of worthlessness, guilt, despair, suicidal thoughts…
- Disruptive behavioral problems: Agitation, opposition, aggression, etc. These are frequent and fluctuating in people with Alzheimer's disease. They can be disruptive, even dangerous for the person and those around them, and negatively impact everyone's quality of life.
How can you remember everything, or almost everything?
Today, studies show that it seems possible to modify the onset of Alzheimer's disease. Researchers are aware of a number of risk factors and environmental factors that can be more or less influenced. A genuine prevention strategy for Alzheimer's disease is emerging. It is with this in mind that Professor Philippe Amouyel, unit director at the Pasteur Institute in Lille, published his book "The Anti-Alzheimer's Guide." It lists preventative advice to implement in order to maximize the chances of avoiding Alzheimer's disease. "Reprogramming our lifestyles for the benefit of our health." Indeed, if the first signs are delayed long enough, we can hope to die without having experienced any symptoms of the disease. The book outlines three main areas of prevention for Alzheimer's disease and, more generally, for the decline in cognitive function inherent to aging.
To begin with, it's essential to use your brain, to train it. The professor explains that the best way to train it is through reading, as reading is incredibly effective for our brain. Other seemingly non-intellectual tasks, such as gardening and traveling, are excellent for our brain. By gardening or planning a trip, our brain anticipates the future. This anticipation allows for conceptualization, which is important for maintaining our brain.
Taking care of it
It is crucial to avoid impacts. This includes both external impacts, such as those from a tackle in rugby or heading the ball in football, and internal impacts. These impacts are not immediate. Initially, we are protected by our blood-brain barrier, which filters out harmful substances, but over time, nicotine and alcohol eventually pass through. Once this barrier is damaged, anything can get through, and we are no longer protected. Taking care of your brain also means not suppressing sneezes and coughs. This may seem amusing, but this advice is quite real. It's important to know that our bodies contain very small blood vessels that transport blood throughout our system, and some of these vessels are less well-formed and can, under the pressure of a suppressed cough, rupture and lose a small amount of blood. While this may not have immediate consequences, over time, these micro-ruptures can lead to the loss of a number of neurons in the brain.
Taking care of one's health
The first fundamental element of our health is hearing. Indeed, we must truly pay attention to our hearing. Not only because it can create a breakdown in social connections, but also because hearing loss alters our brain structures. It is important to get hearing aids when necessary. Next, we must know that our brain's best friend is our heart. Taking care of our heart is paramount. Thus, diet plays a crucial role in mitigating the risk of Alzheimer's disease. Mediterranean diets based on fish, vegetables, fruit, and olive oil are excellent. Then, between the ages of 45 and 65, it is important to be screened for major risk factors: cholesterol levels, diabetes, excess weight, blood pressure, etc. Physical activity is also an essential element of brain health. Without going so far as to talk about sports, it's about moving more, being more mobile. The important thing is not to aim for performance but to engage in physical activity, especially walking. In conclusion, fighting Alzheimer's disease involves interaction. We must live with others. Humans need other people to thrive. Isolation is a significant aggravating factor. Whenever possible, we shouldn't be alone. Being with another person reduces the risk of developing Alzheimer's disease by two to three times. Seeing friends, playing games, going to the movies, having conversations, even arguing—all these activities increase the number of synaptic connections and are therefore beneficial to our brains. Finally, cultivating optimism also helps us fight Alzheimer's disease.
