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The University of Pittsburgh School of Medicine discovered that astrocytes, star-shaped brain cells, are crucial for controlling the pendulum in Alzheimer's disease. Only individuals with an amyloid load and aberrant blood indicators of astrocyte activation or reactivity, according to the team's study, which was published in Nature Medicine, will eventually advance to symptomatic Alzheimer's disease.

Blood samples were tested from more than 1,000 cognitively unimpaired elderly people with and without amyloid pathology. According to Tharick Pascoal, senior author of the study, "Our study argues that testing for the presence of brain amyloid along with blood biomarkers of astrocyte reactivity is the optimal screening to identify patients at risk for progressing to Alzheimer's disease."

"This puts astrocytes at the center as key regulators of disease progression, challenging the notion that amyloid is enough to trigger Alzheimer’s disease," he added.

The most common form of dementia, Alzheimer's disease progresses gradually, beginning with modest memory loss and possibly advancing to the loss of speech and environmental awareness.

Alzheimer's disease is characterized by the development of tau tangles, which develop inside the neurons, and amyloid plaques, protein clumps stuck between brain nerve cells.

For many years, brain specialists believed that the accumulation of tau tangles and amyloid plaques was both the cause of and a sign of Alzheimer's disease. This assumption also led pharmaceutical companies to ignore the significance of other brain processes, such as the neuroimmune system, and to concentrate heavily on drugs that target amyloid and tau.

According to Pascoal's research and other recent discoveries, the catastrophic cascade of neuronal death that causes rapid cognitive decline may be brought on by interference with other brain processes, like increased brain inflammation.

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Pascoal and his team have previously found that inflammation of brain tissue leads to an increase in pathologically misfolded proteins throughout the brain, which is a direct cause of eventual cognitive impairment in persons with Alzheimer's. Researchers found that a blood test could anticipate cognitive decline nearly two years in the future.

Astrocytes, a type of specialized cell, are abundant in brain tissue. Neuronal cells receive nutrition, oxygen, and defense against infections from astrocytes.

"Astrocytes coordinate brain amyloid and tau relationship like a conductor directing the orchestra," lead author Bruna Bellaver said.

Blood samples from older adults without cognitive impairment, who took part in three different studies, were tested for pathogenic tau and glial fibrillary acidic protein (GFAP), a biomarker of astrocyte reactivity. It turned out that only the ones who had positive results for both astrocyte and amyloid reactivity had symptoms of Alzheimer's disease.

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In order to delay the progression of the disease, trials are moving toward earlier and earlier presymptomatic illness phases, making an accurate early assessment of Alzheimer's risk critical to their success. Amyloid positivity by itself cannot determine a person's suitability for therapy because a sizable proportion of amyloid-positive patients will not experience clinical Alzheimer's symptoms.

The use of astrocyte reactivity markers in the panel of diagnostic tests will make it simpler to identify patients who are most likely to develop to the later stages of Alzheimer's disease as a result of the team's innovative study. This will assist in reducing the number of potential candidates for therapeutic approaches that are most likely to be successful and benefit people with Alzheimer's disease in the future.