They identify for the first time a possible genetic cause

For the first time, researchers have identified a genetic form Alzheimer’s disease later in life in people who have inherited two copies of the troublesome gene.

Scientists have long known that a gene called APOE4 is one of many factors that can increase a person’s risk of developing Alzheimer’s disease, including simply as they age. The vast majority of cases of Alzheimer’s disease occur after age 65. But research shows that for people carrying not one but two copies of the gene, it is more than a risk factor; it is a major cause of this mind-bending disease.

The data obtained indicate a difference with “profound consequences”said Dr. Juan Fortea, who led the study at the Sant Pau Research Institute in Barcelona, ​​Spain.

These include: Symptoms may begin seven to 10 years earlier than in other older adults who develop Alzheimer’s disease.

It is estimated that 15% of Alzheimer’s patients carry two copies of APOE4, meaning that in these cases “they can be traced back to a cause, and the cause lies in the genes”– said Fortea. Until now, it was believed that genetic forms of Alzheimer’s disease were only those types that were affected at a much younger age and accounted for less than 1% of all cases.

Scientists say the study makes it critical to develop treatments that target the APOE4 gene. Some doctors don’t offer people with this gene pair the only drug shown to moderately slow the disease, Lekembi, because they are especially prone to dangerous side effects, said Dr. Reisa Sperling, co-author of the Harvard study.

Sperling is looking for ways to prevent or at least delay Alzheimer’s disease, and “this data to me says, wow, what an important group that can be reached before they develop symptoms.”

But this news doesn’t mean people should compete to get a genetic test. “It’s important not to scare everyone who has a family history of Alzheimer’s because this genetic duo is not behind most cases,” he said.

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HOW DOES GENETICS INFLUENCE ALZHEIMER’S DISEASE?

More than 6 million Americans and millions of people around the world suffer from Alzheimer’s disease. Several genes are known to cause rare forms “early appearance”the mutations were passed from parents to children, causing symptoms at an unusually young age, around 50 years old. Some cases are also associated with Down syndrome.

But Alzheimer’s disease most often appears after age 65, especially between ages 70 and 80, and the APOE gene, which also affects how the body deals with fat, has long been known to play a role. There are three main varieties. Most people carry a variant of APOE3, which does not appear to increase or decrease the risk of Alzheimer’s disease. Some carry APOE2, which provides some protection against Alzheimer’s disease.

APOE4 has long been considered the largest genetic risk factor for developing Alzheimer’s disease later in life: two copies are more dangerous than one. It is estimated that about 2% of the world’s population has inherited a copy from each parent.

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STUDY REVEALS CAUSE OF ALZHEIMER’S DISEASE

To better understand the role of this gene, Fortea’s team used data from 3,297 brains donated for research and data from more than 10,000 people participating in Alzheimer’s disease research in the United States and Europe. They examined symptoms and early signs of Alzheimer’s disease, such as sticky amyloid in the brain.

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People with two copies of APOE4 accumulated more amyloid by age 55 than people with one copy or a “neutral” version of the APOE3 gene, they reported in the journal Nature Medicine. At age 65, brain scans showed significant plaque buildup in nearly three-quarters of dual carriers, who were also more likely to have early symptoms of Alzheimer’s disease around this age than between 70 and 80 years.

Fortea said the underlying biology of the disease is remarkably similar to that of younger inherited types.

It’s more like a “familial form of Alzheimer’s disease,” said Dr. Eliezer Masliah of the National Institute on Aging. “This is not just a risk factor”.

It’s important to note that not all people with two APOE4 genes develop symptoms of Alzheimer’s disease, and researchers need to know why, Sperling said.

“It’s not really destiny,” he said.

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HOW THE NEW RESULTS CAN IMPACT RESEARCH AND TREATMENT OF ALZHEIMER’S DISEASE

Lakembi’s drug removes some of the sticky amyloid, but Sperling said it is unclear whether those carrying two APOE4 genes would benefit because they are at very high risk of the drug’s side effect: dangerous inflammation and bleeding in the brain.

One of the research questions is whether they would feel better if they started taking such medications earlier than other people.

Masliah said other research is aimed at developing gene therapies or drugs specifically targeting APOE4. He said it was also important to understand the impact of APOE4 in different populations because it was primarily studied in white people of European descent.

As for genetic testing, at the moment it is usually only used to assess whether someone is a candidate for Lekembi’s treatment or for people participating in Alzheimer’s disease research, especially studies of possible ways to prevent disease. Sperling said that people most likely to carry two APOE4 genes had parents who developed Alzheimer’s disease relatively early, in their 60s rather than their 80s.

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