Recent findings uncovered a blood biomarker that can predict whether or not a person with normal cognitive function would go on to develop Alzheimer's disease.
Researchers at the University of Pittsburgh School of Medicine found that astrocytes, brain cells with a star-like shape, are essential for influencing the pendulum during Alzheimer's disease. The team’s research, published in Nature Medicine, says that only those with a combination of amyloid burden and blood markers of abnormal astrocyte activation, or reactivity, would eventually progress to symptomatic Alzheimer's disease.
More than 1,000 cognitively unimpaired older adults with and without amyloid pathology had their blood tested. "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," says senior author Tharick Pascoal.
"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 continues.
The formation of amyloid plaques, protein clumps stuck between brain nerve cells, and tau tangles, which grow inside the neurons, are the hallmarks of Alzheimer's disease at the tissue level.
Amyloid plaque and tau tangle buildup was thought to be both the cause of and a marker of Alzheimer's disease by brain experts for numerous years. This presumption also caused pharmaceutical companies to focus extensively on compounds that target amyloid and tau, ignoring the importance of other brain functions like the neuroimmune system.
Pascoal's research and other new findings indicate that the catastrophic cascade of neuronal death that results in rapid cognitive loss may be triggered by disruption of other brain functions, such as increased brain inflammation.
In earlier studies, Pascoal and his team discovered that brain tissue inflammation causes pathologically misfolded proteins to increase throughout the brain and is a direct cause of future cognitive impairment in people with Alzheimer's disease. Researchers discovered that a blood test could predict cognitive deterioration nearly two years later.
The brain tissue is rich in specialized cells called astrocytes. Astrocytes provide nourishment, oxygen, and protection from infections to neuronal cells.
"Astrocytes coordinate brain amyloid and tau relationship like a conductor directing the orchestra," shares lead author Bruna Bellaver.
Blood samples from participants in three separate investigations of elderly adults without cognitive impairment were examined for pathogenic tau and glial fibrillary acidic protein (GFAP), a biomarker of astrocyte reactivity. It revealed that only those who had amyloid and astrocyte reactivity results that were both positive displayed signs of Alzheimer's disease.
Trials are advancing to earlier and earlier presymptomatic illness phases to slow the progression of the disease, making an accurate early identification of Alzheimer's risk essential to their success. Amyloid positivity alone cannot indicate a person's eligibility for therapy, as a sizeable portion of amyloid-positive people will not develop clinical manifestations of Alzheimer's.
With the team's novel research, it will be easier to identify patients who are likely to progress to the later stages of Alzheimer's disease by including astrocyte reactivity markers in the panel of diagnostic tests. This will help narrow down the pool of candidates for therapeutic interventions that are most likely to be effective and help the future with Alzheimer's disease.