Alzheimer’s gene present in 26% of the population detected – 10/15/2023 – Health

A study led by Brazilian researchers from UFRGS (Federal University of Rio Grande do Sul) revealed the mechanism behind a genetic marker associated with a greater risk of developing Alzheimer’s.

The article, published on the 25th in the specialized journal Nature Aging, describes how the presence of one or two alleles (as the copies of a given gene are called) of a gene known as Apoe (apolipoprotein E) increases the risk of Alzheimer’s disease. three to 15 times.

This is because, according to research, this gene accelerates the accumulation of beta amyloid and tau proteins in the brain, linked to cognitive decline. The mechanism by which this gene leads to greater protein deposits in the brain is through so-called hyperphosphorylation (addition of a phosphate molecule to the protein).

In a normal state, tau protein has the function of repairing the structure of neurons. In the hyperphosphorylated form, it fails to maintain their structures, leading to cell death.

Furthermore, the presence of one or more forms of this gene also appears to accelerate the accumulation of amyloid protein plaques. According to the study, these are the main factors responsible for causing brain damage and cognitive decline associated with Alzheimer’s.

The findings are important as they can help in the detection of patients with initial symptoms of Alzheimer’s, since the patient who carries the gene can discover it through a blood test.

The doctoral student in the biochemistry department at UFRGS and medical student at the university, João Pedro Ferrari Souza, explains that 25% of the population has one copy of the gene, and 1%, both, thus representing more than a quarter of the population. population at high risk for dementia.

He makes a reservation, however, that the presence of this copy is not equivalent to cases of Alzheimer’s of hereditary origin, that is, whose gene linked to the condition was passed on to descendants, which represents approximately 10% of cases.

The research was part of Souza’s so-called sandwich period in the United States, when the postgraduate student spends a year at a foreign institution, under the guidance of Eduardo Zimmer, from UFRGS, and Tharick Pascoal, from the University of Pittsburgh (USA). Researchers from McGill University, in Canada, and the University of Gothenburg, in Sweden, also participated.

Over a two-year period, 94 Alzheimer’s patients were evaluated from a study group called Triad (translational biomarkers in aging and dementia, in free translation), at McGill University, in Canada.

Participants were subjected to four different analyzes to verify the presence of the ε4 variants of the Apoe gene (read epsilon 4 variant of the apolipoprotein E gene): liquor (brain fluid in the skull-brain barrier), blood, magnetic resonance imaging tests and PET-amyloid, a type of tomography specific for amyloid plaques.

Scientists saw that the presence of the Apoeε4 allele enhances the harmful effects of the amyloid beta protein. “In other words, Apoeε4 accelerated the effect that amyloid had on the accumulation of tau protein. Individuals who had one allele had a 3 to 4 times greater risk of developing Alzheimer’s, and the two alleles, 12 to 15 times, compared with individuals who did not carry it”, says Souza.

According to him, the new drugs recently approved for the treatment of the initial phase of Alzheimer’s, such as donanemab, from Eli Lilly, and lecanemab, from the company Biogen, whose action is precisely in the formation of amyloid plaques, can be combined with the new discovery .

“We believe that the ideal would be, in these people, to combine therapies, that is, you do an exam to determine that they have the genetic marker, the Apoeε4 gene, and then you can know what the patient’s specific benefit will be with the new drugs,” he explains.

The drugs are not yet available in Brazil. Eli Lilly has not yet requested registration of its drug with Anvisa (National Health Surveillance Agency). Until the beginning of this semester, there was also no deadline for when lecanemab could arrive in the country.

For now, the medications available in the country for treating Alzheimer’s are anticholinesterases (donepezil, galantamine and rivastigmine) and memantine, aimed at reducing symptoms.

And, in addition, clinical trials of the drugs showed important, although rare, side effects, such as edema (swelling) and brain hemorrhages.

However, Souza is confident that his team’s discovery could even help pave the way for new studies for drug development.

“These findings help in understanding this important neurodegenerative condition which, by 2030, is expected to affect more than 100 million people worldwide, with direct implications for the treatment of Alzheimer’s disease,” he said.