People with Down syndrome experience accelerated aging and a high incidence of Alzheimer's disease in old age. Researchers from the University of São Paulo (USP) used nuclear medicine techniques to map the presence of neuroinflammation and an important marker of this type of dementia in this population: beta-amyloid plaque – formed by fragments of amyloid peptide that are deposited between neurons, causing inflammation and interrupting neural communication.
“This was the first study in the world to observe how neuroinflammation occurs in this population using positron emission tomography [PET, na sigla em inglês]using specific radiopharmaceuticals,” Daniele de Paula Faria, a researcher at the Nuclear Medicine Laboratory (LIM43) at the Hospital das Clínicas of the USP School of Medicine (HC-FM-USP), told Agência FAPESP.
The investigation was conducted within the scope of a developed in partnership with the Jô Clemente Institute, which allowed researchers to evaluate the brains of individuals with Down syndrome of different age groups.
“It was already known that the aging process in this population occurs about 20 years earlier, with early menopause and the diagnosis of Alzheimer's disease after the age of 40, for example. An important aspect is that the gene for the amyloid precursor protein [APP] is located on chromosome 21, which is tripled in Down syndrome. Therefore, it was already known that these individuals produce more beta-amyloid than those without the syndrome. Our study was important, because there was still no in-depth understanding of the patterns of neuroinflammation in the living brains of people with Down syndrome,” the researcher explained to FAPESP Agency
The researchers also monitored the progression of neuroinflammation and beta-amyloid plaques over two years in mice genetically modified to develop a condition similar to Down syndrome. It is worth remembering that the life cycle of rodents is shorter than that of humans, and therefore a two-year-old animal would be equivalent to an 80-year-old human.
“We were able to assess the progression of the disease in rodents using equipment specifically designed for small animals. The study with mice, combined with the study conducted with the group of individuals with Down syndrome, provides us with important answers about the aging process in this population,” said the researcher.
Inside the brain
These unpublished data were presented by Faria during the Molecular Imaging Symposium, held on September 11 and 12 at the Radiology Institute of HC-FM-USP. One of the objectives of the event was to celebrate the tenth anniversary of the first amyloid image obtained in Brazil, which was possible with the purchase of equipment that produces radiopharmaceuticals ( C-GDP and C-PK11195) used to visualize plaques and neuroinflammation in the living human brain. Acquisition occurred using a led by Geraldo Busatto Filho, coordinator of LIM21 ( read more at:
As Faria explains, molecules labeled with radioisotopes (called radiopharmaceuticals) are injected into the brain to signal the regions where there is an accumulation of beta-amyloid peptide. It is then possible to visualize the plaques and the progression of neuroinflammation using positron emission tomography, an imaging device similar to magnetic resonance imaging.
The methodology was validated in Brazil by the USP group and, combined with other analyses, constitutes an important tool for differentiating cases of Alzheimer's disease from other types of dementia. It also allows studying how the disease progresses in specific populations, such as individuals with Down syndrome or multiple sclerosis.
In his closing lecture at the symposium, Marco Antonio Zago, president of FAPESP, stated that the project is an example of the solidity of science produced in the State of São Paulo. “This is essentially due to three factors. One of them is stable funding. This stability allows us to carry out ten-year research programs that can yield advances, set us apart and strengthen the development of the State. The second point is the body of qualified researchers. The third is that we have institutions of excellence, such as the universities and research institutes that have played a major role in the history and development of São Paulo. All of this makes the support structure for science and technology stand out and can serve as an example for the rest of the country,” he said.
The president of the Foundation also presented research funding opportunities, especially for the young scientists who participated in the event. “We are currently experiencing a crisis in the training of human resources and a crisis in the interest of our young people in university life. So it is very good to have a conversation about funding possibilities to attract talent and new important projects,” he added.
In addition to celebrating ten years since the beginning of amyloid PET imaging in Brazil and presenting the results obtained during the period using the technique, the symposium aimed to discuss the most current aspects of molecular neuroimaging research in neurodegenerative diseases with national and international experts.
Among those present were Tharick Pascoal, from the University of Pittsburgh School of Medicine (United States), who spoke about the use of biomarkers in research; David Jones, from the Mayo Clinic (United States), who discussed the use of artificial intelligence in molecular imaging studies; and Juan Fortea, from the Hospital de la Santa Creu i Sant Pau (Spain), who explained how Down syndrome can be a study model for neurodegenerative diseases.
This content was originally published in Researchers map Alzheimer's risk in people with Down syndrome on the CNN Brasil website.
Source: CNN Brasil