Signs of Alzheimer’s show up long before diagnosis, Harvard experts say

The scientists identified changes in the functional organization of the brain years before cognitive decline occurs. How it could impact the treatment of the disease

The researchers found that plasma concentrations of 2-amino-ethyl dihydrogen phosphate and taurine. Photo: Shutterstock.

As life expectancy increases around the world, so does the number of people living with dementia. Globally, more than 55 million people (8.1% of women and 5.4% of men over 65 years of age) live with this mental illness, according to data from the World Health Organization (WHO). ). Furthermore, this number is estimated to increase to 78 million by 2030 and 139 million by 2050.

the disease of Alzheimer’s It is a neurological disorder that causes brain atrophy and generates the progressive death of neurons. It is the most common cause of dementia, causing ongoing deterioration in thinking, behavior, and social skills that affects a person’s ability to live independently.

Recently, an investigation by Harvard experts pointed out that the Alzheimer’s could be detected many years before the onset of cognitive damage. The new study led by researchers at Massachusetts General Hospital, associated with Harvard University Medical School, showed that early accumulation of tau and amyloid-ß proteins can disrupt brain connectivity many years before signs of deterioration, such as memory loss or recurrent forgetfulness, are seen The findings may lead to strategies that could help detect Alzheimer’s disease Alzheimer’s early.

Researchers have known for years that amyloid-ß and tau pathology, the hallmarks of Alzheimer’s disease Alzheimer’scan cause the death of neurons, the most abundant cells in the brain, leading to cognitive decline and dementia.

“However, we did not know how the brain’s connections respond to the accumulation of these proteins very early in the disease process, even before symptoms,” explained Yakeel Quiroz, lead author of the article published in Proceedings of the National Academy of Sciences.

In their research, the scientists used positron emission tomography (PET) for tau and amyloid-ß, and functional magnetic resonance imaging (fMRI) to study how Alzheimer’s disease pathologies Alzheimer’s were related to the connectivity of brain regions and networks in individuals from a large family of more than 6,000 living members with a prevalence of Alzheimer’s disease. Alzheimer’s of Antioquia, in Colombia.

Researchers at Massachusetts General Hospital have formed a unique relationship with this Colombian family over the years, ultimately creating the COLBOS study (Colombia: Boston) in 2015 in conjunction with the Fundación Universidad de Antioquia, with the goal of investigating how disease progresses before cognitive decline sets in and find sensitive biomarkers to predict who is at high risk for dementia.

Among all the members of the Colombian family studied, the researchers detected that 1,500 carry an autosomal dominant mutation (known as Presenilin-1 E280A), so they estimate that these carriers will develop the disease Alzheimer’s early-onset, with almost 100% certainty, and have a well-characterized disease course, with mild cognitive impairment (MCI) at a mean age of 45 years and dementia at 51.

Previously, the same research team showed that people exhibit high levels of amyloid-ß almost two decades before the onset of mild cognitive impairment, and tau pathology about six years before onset. “Studying this unique population can really help us understand how amyloid-ß and tau pathology might affect the way the brain communicates years before people develop dementia,” said study co-author Edmarie Guzmán-Vélez.

The team used MRI scans to examine brain regions at the voxel level, pixel-like representing 3D units spanning millions of brain cells, to look at connectivity between different brain networks.

Through extensive analysis, they found that the mutation carriers showed disruptions in connection in the brain’s main memory network years before the onset of cognitive decline in the family. The researchers also developed a novel mathematical approach that combines fMRI and molecular imaging to see more clearly when brain regions start to shut down during the disease process.

“This mathematical approach showed how the functional disconnectivity of a memory network was explained by the early stages of tau pathology,” explained Ibai Diaz, co-author of the report. These findings suggest that functional disconnections are evident once tau begins to accumulate in the brain and before brain atrophy, a sign of neurodegeneration, is detected.

“This discovery improves our understanding of how disease-related pathology Alzheimer’s it alters the functional organization of the brain years before cognitive decline occurs,” said Quiroz, who is director of the Massachusetts General Hospital Familial Dementia Neuroimaging Laboratory and the Multicultural Program for the Prevention of Dementia. Alzheimer’s.

For the specialist, “these findings are exciting because they also suggest that functional magnetic resonance imaging could be used in the future to identify people who may already have the pathology of Alzheimer’s disease. Alzheimer’s and they may develop dementia in the future, although more research is still needed.”

The researchers hope their results will highlight the level of urgency and importance of preclinical and clinical trials for Alzheimer’s disease. Alzheimer’sparticularly those aimed at disease prevention.

“We now know that there are many things going on in the brains of people at risk of Alzheimer’s disease. Alzheimer’seven before signs of memory impairment appear, so we hope that findings like these could improve our understanding of preclinical AD and help improve the selection of those who would benefit most from participating in clinical trials.”

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