Antioquia is a fertile region, with as many roads between its mountains as the furrows that vanish from the brain of its inhabitants. But in Colombia, the inhabitants do not know that it is also the place of origin of a genetic mutation that causes Alzheimer’s early. This is the ‘Paisa mutation’. The discovery of this anomaly was made possible thanks to Dr. Francisco Lopera Restrepo, a Colombian neurologist who has devoted little more than 3 decades to the study of Alzheimer, recognized as the main cause of dementia, a condition that-according to the latest report of the (Adi, Alzheimer’s Disease International) affects 50 million people in the world. Of this number of people affected, 25 families and more than 6 thousand members are at risk of developing the disease of Alzheimer’s disease because of Family start early.
More than 30 years ago when I was a neurology resident, I had the opportunity to detect a family with several cases of people affected with the same disease, an early onset Alzheimer’s. That is to say that they were people who were beginning to lose the memory to 45 years. At that time I was struck by the very early age of this memory loss, considering that Alzheimer’s dementia usually begins after age 65,” the specialist says. Early onset family Alzheimer’s or ‘Paisa mutation’ is an inherited form of Alzheimer’s disease that is usually initiated very early, with a very large focus of affected families in Colombia, especially in Antioquia.
One of the particularities is that 50% of the descendants of people with the disease will also suffer from the genetic mutation.
The disease, as Dr. Lopera explains, is caused by the accumulation of residues in a protein waste called amyloid in the body. “There is an abnormality in the metabolism of a large protein called amyloid precursor protein. That protein is normal in the body but because of the genetic mutation this protein is poorly metabolized, poorly cut and produces an insoluble and toxic fragment. These fragments adhere to each other and form the amyloid plates that are seen in the brain in a person who dies with the disease.“ According to Lopera, it is believed that this mutation comes from Europe, was established in this region of the country and then spread to other countries, such as Australia, the United States and Spain, due to the migration of antioquians. “It’s funny that it hasn’t been reported in other parts of the world, but we’ve already analyzed the genome of people who have this disease and everyone who has the mutation has a part of the European genome,” the researcher said.
Sought cure at the most advanced stage of the disease
From Medellín, Dr. Lopera serves as coordinator of the Neuroscience Group at the University of Antioquia. It is also the principal investigator in an international project known as API Colombia, an acronym for Alzheimer’s Prevention Initiative (Initiative for the prevention of alzheimer’s) that is currently conducting a study on the prevention of alzheimer’s disease on the basis of the affected population with the variety of alzheimer’s disease genetic previously described.
The study began in 2013 and will end in 2022. In a population of 25 families, with more than 6,000 heirs. 252 healthy people between the ages of 30 and 60 have entered the experimental study of this population group, who are being treated from 2013 to 2022, year of completion of the research to evaluate and answer the question of whether this medicine is able to prevent or delay the onset of the disease. A medicine that cleans the brain of amyloid is currently being used. For now, it is only being used in healthy people, descendants of these families with high genetic risk for having inherited the mutation and who will inevitably develop Alzheimer’s disease. Because amyloid deposits begin 25 years before starting the first symptoms, the idea is to act with that drug on that junk protein, remove it from the brain, and look for the possibility that in this way we can prevent or delay the onset of symptoms of the disease. “This medicine is known to be effective in removing these plates. Now, what we don’t know is if it’s enough to remove those plates to prevent the disease. That’s the question we have to solve.”
It should be noted that Alzheimer’s disease does not only depend on the formation of amyloid plates. Other factors are also involved in its development, such as the tau protein deposit, another protein waste that is deposited in the body but much later, compared to the beginnings of the amyloid deposit. “The amyloid in the families of Antioch begins to deposit at the age of 28. Instead, tau protein begins to deposit at age 38, “explains Lopera,” in such a way that we believe that if we clean amyloid before age 38, we could prevent TAU also from being deposited because we are not using an anti-TAU medication. But that is a hypothesis that we must analyze when the study is finished.”
To receive a diagnosis of Alzheimer’s, the person must have experienced a decline in cognitive or behavioral function and performance compared with how they were previously. This decline must interfere with their ability to function at work or in usual activities.
The cognitive decline must be seen in at least two of the five symptom areas listed below:
- Reduced ability to take in and remember new information, which can lead, for example, to:
- repetitive questions or conversations
- misplacing personal belongings
- forgetting events or appointments
- getting lost on a familiar route
- Impairments to reasoning, complex tasking, and exercising judgment, for example:
- poor understanding of safety risks
- inability to manage finances
- poor decision-making ability
- inability to plan complex or sequential activities
- Impaired visuospatial abilities that are not, for example, due to eye sight problems. These could be:
- inability to recognize faces or common objects or to find objects in direct view
- inability to use simple tools, for example, to orient clothing to the body
- Impaired speaking, reading and writing, for example:
- difficulty thinking of common words while speaking, hesitations
- speech, spelling, and writing errors
- Changes in personality and behavior, for example:
- out-of-character mood changes, including agitation, apathy, social withdrawal or a lack of interest, motivation, or initiative
- loss of empathy
- compulsive, obsessive, or socially unacceptable behavior
If the number and severity of symptoms confirm dementia, the following factors can then confirm Alzheimer’s.
- a gradual onset, over months to years, rather than hours or days
- a marked worsening of the individual’s normal level of cognition in particular areas
If symptoms begin or worsen over the course of hours or days, you should seek immediate medical attention, as this could indicate an acute illness.
Alzheimer’s is most likely when memory loss is a prominent symptom, especially in the area of learning and recalling new information.
Language problems can also be a key early symptom, for example, struggling to find the right words.
If visuospatial deficits are most prominent, these would include:
- inability to recognize objects and faces
- difficulty comprehending separate parts of a scene at once
- difficulty with reading text, known as alexia
The most prominent deficits in executive dysfunction would be to do with reasoning, judgment, and problem-solving.
Types of Alzheimer’s
It is a disorder that can be associated with different causes; thus, we can differentiate three types of Alzheimer’s.: Alzheimer’s family: it is known that people in whose family there have been cases of Alzheimer’s are more likely to have the disease. In addition, there is a type of Alzheimer’s specifically called family alzheimer’s, which is characterized by early onset, i.e. before age 60. This type of alzheimer’s disease is due to mutations in genes such as the gene for the amyloid precursor protein, the gene of the presenilin I or the gene of the presenilin II. Mutations in these genes lead to an abnormal cluster of beta amyloid protein, the main component of the senile plates.
This type of family Alzheimer’s disease is rare. Alzheimer’s disease is associated with the Down syndrome: due to trisomy on chromosome 21, people with this syndrome have an excess of amyloid precursor protein, which favors its metabolism leads to an accumulation of the fragments causing the senile plaque. In individuals with Down syndrome we find cases of Alzheimer’s from the age of 12. Alzheimer’s associated with age: although this disease is not a consequence of aging, it affects 5-7% of people over 65 years of age. There are more than 70 genes whose presence in the body may encourage the appearance of Alzheimer’s associated with age. These include the gene for the ubiquitin, the protein tau gene, or the gene of the apolipoprotein E. In any case, the altered metabolism of the amyloid precursor protein is involved in all types of Alzheimer’s described.
The progression of Alzheimer’s can be broken down into three main stages:
- preclinical, before symptoms appear
- mild cognitive impairment, when symptoms are mild
In addition, the Alzheimer’s Association describes seven stages along a continuum of cognitive decline, based on symptom severity.
The scale ranges from a state of no impairment, through mild and moderate decline, eventually reaching “very severe decline.”
A diagnosis does not usually become clear until stage four, described as “mild or early-stage Alzheimer’s.”