‘Cursed’ line of early Alzheimer’s disease sheds light on ways to protect against the disease | Health and wellness

A curse of sorts seemed to hang over a handful of families in Juramala, a municipality in the Antioquia region of northwestern Colombia. For generations, its inhabitants believed that a spell had fallen on their heads and doomed them to the oblivion of youth, since many of them began to lose their memory as soon as they turned 40 years old. However, just over three decades ago, science managed to dispel superstition and illuminate the true reason for such a life sentence: thousands of people from 25 families had the so-called paisa mutation – a variation of the presenilin 1 gene, which causes its carriers to develop early-onset Alzheimer’s disease with almost 100% probability.

This discovery has opened the door to research into treatments that can reverse or at least delay the onset of this neurodegenerative disease at such an early age. And it has turned this Colombian territory into the epicenter of the scientific battle against early-onset Alzheimer’s disease. The research had, in fact, already identified a patient who was almost immune to hereditary dementia and found that this was because, despite the woman being a carrier of the paisa mutation, she had two copies of the gene. APOE 3 Christchurchvery rare gene variant APOE 3 which appears to protect against the development of the disease. Now a new study is published this Wednesday in the journal New England Journal of Medicine advances understanding of this mechanism and confirms that even one copy of this protective genetic variant is sufficient to help delay cognitive decline.

About 55 million people worldwide suffer from dementia, with Alzheimer’s disease being the most common form. It is a neurodegenerative disease that usually camouflages itself in the body for decades: it begins to spread silently 20 or 30 years before it shows symptoms, and by the time it shows its face, it is usually already at a very advanced stage. There is no cure or medication that can stop its progression. At best, they manage to moderately delay the progression of some symptoms, but do not control the disease. In Spain, approximately 800,000 people suffer from Alzheimer’s disease.

Two proteins, beta-amyloid and tau, accumulate in the brains of sick people and poison neurons until they kill them. The exact cause of Alzheimer’s disease is not clear, but the scientific community has been able to identify genes and variants that may protect or predispose to the disease. Like the paisa mutation condemning early emergence, or APOE 3 Christchurch, showing some protection. He APOE, In fact, it is this gene that most strongly contributes to the development of Alzheimer’s disease, although there are three variants: 2 reduces the risk of the disease, 4 significantly increases it, and 3 is more or less neutral.

In the case of the Colombian patient with resistant Alzheimer’s disease, the medical tests they performed showed that her brain was full of amyloid protein, but she had very low levels of tau, and she reached the age of 70 without clinical traces of the neurodegenerative disease. The reason for this resistance, which scientists discovered, was the gene APOE 3 Christchurch, which gave him a kind of temporary protection from the devastating disease: his neurons remained functional longer, and he developed Alzheimer’s disease only three decades later than expected. Another investigation last year identified a second exceptional case: a man with the Pais mutation who, however, did not experience cognitive decline until he was 67 years old. In this case, the patient was not a carrier of the protective variant. APOE 3 Christchurch, but they found a mutation in the gene that expresses Reelin, a protein that competes with APOE to bind to the same receptors on brain cells.

Taking a new step forward in research on this particular population in the Antioquia region, researchers discovered that a single copy of the gene APOE 3 Christchurch This is enough to help delay the cognitive decline that begins the disease. From a cohort of 1,077 people with the paisa mutation, the scientists identified 27 people who also had a copy of this very rare protective variant and analyzed their health progress. The study found that cognitive decline in this group began at around age 52, whereas in people without the gene APOE 3 Christchurchthe age of onset of cognitive problems was 47 years.

Less accumulation of tau protein

The study describes some cases, such as the case of a man who carried a copy of the gene. APOE 3 Christchurch, who at age 47 had no cognitive problems and his neurological tests were normal. He was not diagnosed with mild dementia until he was 54 years old. In his case, he also had greater accumulation of amyloid beta in the brain, but levels of these tau protein tangles, which also characterize the development of Alzheimer’s disease, were much lower than expected at this age in people with the Pais mutation. . This pattern was also reported in four autopsies performed on other study participants.

Protective genetic copy effect APOE 3 Christchurch This resulted in less pathological damage associated with tau exposure, less neurodegeneration, and a delayed age of onset of cognitive impairment, although less than in a patient with two copies of the strange variant. “(Having a single copy APOE 3 Christchurch) “delays the onset of cognitive decline in a form of autosomal dominant Alzheimer’s disease and may have a protective effect against Alzheimer’s disease and neurodegeneration in this population,” the authors note in the paper.

Juan Fortea, a neurologist at Sant Pau Hospital, insists that the study, in which he was not involved, is “relevant work.” “The presence of two copies of this gene was very suggestive that it had a protective function. We now know that carrying one copy also has a protective effect. Fewer, but they are there. The main thing is to understand how mutations occur APOE 3 Christchurch They are protective because if we understand the mechanisms, we can try to mimic them with a drug,” he explains. Fortea and his team also recently identified a new form of genetic Alzheimer’s disease, finding that virtually all people with two copies of the gene APOE 4 develop biomarkers associated with dementia.

In statements to the scientific portal Science Media Center (SMC), Jordi Pérez-Tur, senior researcher at the Institute of Biomedicine of Valencia-CSIC, emphasizes that deciphering the mechanisms that make a person slightly resistant to disease progression makes it “achievable.” Find some way to slow the progression of the disease: “We are faced with discoveries with a very important aspect that just recently could not be so clearly seen: there are ways to slow the progression of Alzheimer’s disease. Although the authors limit this option to APOE for the Colombian family, data presented by other authors predict a moderate effect of the variant APOE 3 Christchurch may occur in the general population.”

Fortea is aiming to investigate the presence of this very rare protective variant in other populations with a high susceptibility to Alzheimer’s disease, such as people with Down syndrome or people who have two copies of the APOE 4 gene. “It is a very rare variant, but it is a very rare variant. this does not mean that it does not provide us with mechanisms that can serve on a general level. Sometimes studying rare, unusual cases provides clues that may have general application,” he reflects.

You can follow EL PAIS Health and Wellness V Facebook, X And instagram.