Key to predicting whether a healthy adult will develop Alzheimer’s

The accumulation of toxic amyloid beta protein in the brain and the formation of tau tangles within neurons are characteristic of the Alzheimer’s, which have also long been considered to be to blame for its appearance. For this reason, to prevent or stop this disease, drugs have been created that target amyloid and tau, without taking into account other brain processes that may also be involved, such as the neuroimmune system.

However, there is scientific evidence showing that many people whose brains contain a large number of plaques or amyloid tangles do not develop the disease. For this reason, scientists continue to look for differentiating elements that make some individuals more or less prone to dementia.

A new investigation has been able to find the solution to this enigma because it has discovered that astrocytes – a type of star-shaped brain cells – are responsible for tipping the scales in favor or against the progression of Alzheimer’s. The researchers analyzed blood samples from 1,016 older adults without cognitive decline (with a mean age of 69.6 years), with and without amyloid pathology, and verified that only those who had a combination of amyloid load and blood markers of abnormal activation or reactivity of astrocytes They developed Alzheimer’s symptoms later.

“The presence of brain amyloid in conjunction with blood biomarkers of astrocyte reactivity is the optimal screening test to identify patients at increased risk for Alzheimer’s.”

The results have been published in Nature and they can contribute to the development of new therapies capable of stopping the progression of this type of dementia. “Our study argues that testing for the presence of brain amyloid in conjunction with blood biomarkers of astrocyte reactivity is the optimal screening test to identify patients at increased risk of progressing to Alzheimer’s disease,” says Dr. Tharick Pascoal, associate professor of psychiatry and neurology at the University of Pittsburgh School of Medicine and lead author. “This puts astrocytes at the center as key regulators of disease progression, challenging the notion that amyloid is enough to trigger Alzheimer’s disease.”

Brain processes involved in Alzheimer’s disease

In a previous study published in Nature Medicine Dr. Pascoal and his team found that inflammation of brain tissue triggers the pathological spread of misfolded proteins in the brain and is a direct cause of the cognitive decline experienced by Alzheimer’s disease patients. In their new job, they have discovered that cognitive decline can be predicted by a blood test.

Astrocytes are immune cells found in brain tissue that provide oxygen and nutrients to neuron cells and protect them against pathogens, but because they don’t conduct electricity, they didn’t appear to influence the way neurons communicate with each other. and for this reason they were not considered to play a role in health and disease, but in this latest research they have been taken into account.

“Astrocytes coordinate the relationship between brain amyloid and tau like a conductor conducting the orchestra,” explained the study’s lead author, Bruna Bellaver, a postdoctoral associate at Pitt. “This may be a game changer in the field, as glial biomarkers are generally not considered in any major disease model.”

The researchers analyzed blood samples from older people without cognitive impairments to look for biomarkers of astrocyte reactivity (glial fibrillary acidic protein, or GFAP) along with the presence of pathologic tau. The results revealed that only those who tested positive for both amyloid and astrocyte reactivity showed evidence of progressively developing tau pathology, indicating a predisposition to clinical symptoms of Alzheimer’s disease.

These findings have great relevance for the design of future clinical trials to test drug candidates for the Alzheimer’s treatment. The goal of scientists is to detect and stop the disease in its early stages, when symptoms have not yet appeared. Because a significant percentage of amyloid-positive individuals will not progress to clinical forms of this dementia, amyloid positivity alone is not sufficient to determine the best person to try a potential therapy.

For this reason, including markers of astrocyte reactivity, such as GFAP, among diagnostic tests will allow better selection of patients most likely to progress to later stages of Alzheimer’s, and thus help refine the selection of candidates who will obtain greater benefits when undergoing therapeutic interventions.


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