Extra Credit

Advancing Against Alzheimer’s

Pitt Researchers have identified a new culprit in Alzheimer’s progression — a development that could help change the prevention and treatment of the disease.
Photography by
Aimee Obidzinski/Pitt Photography

two people in front of brain scans

Two older adults check in at the hospital to undergo brain scans. Their results are remarkably similar. Both show an accumulation of amyloid plaques—proteins that clog the spaces between neurons and serve as a telltale sign of Alzheimer’s disease. But, as time passes, only one of the patients experiences a steep cognitive decline. The other patient remains as sharp as the day the scan occurred. 

Doctors have long struggled to explain why two patients with nearly identical indicators end up with starkly different outcomes. Researchers at Pitt’s School of Medicine may have finally pinpointed an answer, one that has upended their understanding of Alzheimer’s progression and could have a profound effect on its treatment. 

Until this study, led by Associate Professor of Psychiatry and Neurology Tharick Pascoal and recently published in the journal Nature Medicine, clinical studies focused on the buildup of amyloid plaques between neurons and the development of tau, another protein, inside neurons as not just indicators of Alzheimer’s disease but also its sole cause. 

“It made sense,” Pascoal says. “Neurons carry the information; they’re the main cells in the brain. But now we’re looking at these other cells— astrocytes—and we believe they are an integral part of Alzheimer’s.” 

Astrocytes, as the name suggests, are star-shaped cells responsible for maintaining healthy brain function by providing neurons with nutrients and protecting them from pathogens. But when Pascoal’s team tested the blood of more than 1,000 cognitively healthy people—some with amyloid plaques and some without—they found amyloid alone couldn’t predict whether patients would develop symptoms of the disease. Only those with an accumulation of amyloid and abnormality of a blood biomarker called GFAP, which points to atypical activity in astrocyte cells, experienced cognitive decline. 

It suggests astrocytes are actually key to Alzheimer’s progression. 

“We know astrocytes are responsible for maintaining every function, or most of the functions, in a healthy brain,” says Bruna Bellaver, the study’s lead author and a postdoctoral associate at Pitt. “For us, it made sense, then, to say, ‘Maybe dysfunction in these cells is an important trigger for the disease. Maybe people who have amyloid pathology but have these cells working properly can maintain a healthy environment in the brain.’” 

Bellaver hopes to one day study why some astrocyte cells behave atypically and determine if this plays a role in other neurodegenerative diseases. But, for now, being able to detect the abnormal activity with a blood test is enough to potentially shape the future of Alzheimer’s treatment. 

The most direct impact of such a development is likely to be felt in clinical trials. Researchers are testing medications that target the earliest stages of the disease in presymptomatic patients with amyloid plaques, not knowing who will go on to develop symptoms and who will not. The biomarker will allow researchers to narrow the pool of patients by identifying those who will progress and ultimately benefit from the treatment. 

And it’s not the only upshot of research by Pascoal and his team. He believes, with further studies and development, the blood biomarker could eventually make Alzheimer’s testing less expensive and more accessible. 

“We have a vision for Alzheimer’s. We’re not there yet—but we’re working so that one day, you can arrive at your primary care physician and that physician can order blood tests for liver function, for kidney function, and also be able to test for Alzheimer’s disease,” Pascoal says. “Seeing how your cognition will change in the coming years will become a big part of a patient checkup.”

This story was published Aug. 29, 2023. It is part of Pitt Magazine's fall 2023 edition.