Researchers at the University of Pittsburgh report that by using blood tests, they have identified a key clue for determining who is likely to develop Alzheimer’s disease.
Their method relies on blood biomarkers of star-shaped brain cells, called astrocytes. By searching for signs of astrocyte reactivity, in conjunction with other diagnostic tests, the researchers found they can predict whether a cognitively unimpaired person will progress to symptomatic Alzheimer’s.
“During normal conditions, [astrocytes] are cells that keep our brains functioning normally. … But when they are under some threat in the brain, then they are over-activated, and they work more to try to compensate [for] dangers in the brain,” said lead author of the study Bruna Bellaver, a postdoctoral associate at Pitt.
The academic journal Nature Medicine published her research team’s results Monday. The article’s authors include more than a dozen scientists at Pitt’s School of Medicine, in addition to researchers from the University of Gothenburg in Sweden, McGill University in Canada, and the University of Illinois in Chicago.
Their discovery marks a major breakthrough in the vexing battle against a neurological disorder that affects more than six million people in the United States. Alzheimer's is a form of dementia that usually occurs in people aged 65 or older. It typically begins with mild memory loss and in later years tends to impair a patient’s ability to carry on a conversation and respond to their environment.
The Alzheimer’s Association reports that on average people with the disease live between four and eight years following diagnosis, although some live as long as 20 years.
Bellaver said that with the technique she and colleagues have developed, doctors can screen patients as young as 50 years old for astrocyte reactivity.
“The great advantage of diagnosing these patients using blood [is that] it's very easily accessible,” Bellaver noted. To detect other signs of Alzheimer's, she said, doctors must use PET scans, a costly imaging technology.
For decades, scientists have focused their efforts to screen for Alzheimer’s on methods that detect a build-up of amyloid plaques between nerve cells of the brain. They also look for clumps of other proteins, called tau tangles, that form inside the neurons.
But Pitt’s new study reveals how another brain process could be just as important in triggering neurological decline. It included more than 1,000 cognitively unimpaired people whose brains had and had not developed an accumulation of amyloid plaques.
Astrocytes are brain immune cells that supply neuronal cells with nutrients and oxygen while protecting them from pathogens, Pitt said in a statement announcing the study’s publication. The new research shows that only people who demonstrated both amyloid and astrocyte reactivity showed evidence of progressively developing tau pathology. As a result, they were more likely to develop clinical symptoms of Alzheimer’s disease. A significant number of amyloid-positive individuals will never progress to clinical forms of Alzheimers, Pitt noted in its statement.
“Astrocytes coordinate [the] brain amyloid and tau relationship like a conductor directing the orchestra,” Bellaver said in the statement. Because evidence of over-activation among astrocytes could reflect their effort to combat damage caused by amyloids, Bellaver said her team’s findings could be a “game-changer” for the fight against Alzheimer’s. She noted that researchers still must validate the findings.
Pitt said in a statement that the continued study of astrocyte reactivity will have implications for future clinical trials of Alizheimer’s drug candidates by facilitating earlier diagnoses of the disease. In July, physicians at UPMC will have the option to screen patients for astrocyte reactivity as part of Pitt’s research into the phenomenon’s medical applications.
