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Blood biomarker can help predict Alzheimer’s - study

New research has revealed further details of how Alzheimer’s disease is caused, and a blood test could predict who will go on to develop the condition. A new paper published in Nature Medicine by staff at the University of Pittsburgh School of Medicine found that the build-up of amyloid protein in the brain, long associated with the disease, may in itself not be enough to cause symptoms.

Patients who went on to develop Alzheimer’s disease were found to be those who also had indicators in the blood that immune cells called astrocytes were activated. Researchers tested the blood of 1,000 elderly people without Alzheimer’s symptoms, some of whom had amyloid build-up, and followed them over time to find out who developed the condition. The team found that only those who had a combination of amyloid burden and blood markers of abnormal astrocyte activation, or reactivity, would progress to symptomatic Alzheimer’s in the future, a critical discovery for drug development aimed at halting progression.

“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 who are most at risk for progressing to Alzheimer’s disease,” said senior author Tharick Pascoal, MD, PhD, Associate Professor of Psychiatry and Neurology at University of Pittsburgh School of Medicine. “This puts astrocytes at the centre as key regulators of disease progression, challenging the notion that amyloid is enough to trigger Alzheimer’s disease.”

At the tissue level, the hallmark of Alzheimer’s disease is an accumulation of amyloid plaques—protein aggregates lodged between nerve cells of the brain—and clumps of disordered protein fibers, called tau tangles, forming inside the neurons. For many decades brain scientists believed that an accumulation of amyloid plaques and tau tangles is not only a sign of Alzheimer’s disease but also its direct culprit. This assumption also led drug manufacturers to heavily invest into molecules targeting amyloid and tau, overlooking the contribution of other brain processes, such as the neuroimmune system.

Recent discoveries by groups like Pascoal’s suggest that the disruption of other brain processes, such as heightened brain inflammation, might be just as important as amyloid burden itself in starting the pathological cascade of neuronal death that causes rapid cognitive decline. In his previous research, Pascoal and his group found that brain tissue inflammation triggers the spread of pathologically misfolded proteins in the brain and is a direct cause of eventual cognitive impairment in patients with Alzheimer’s disease. Now, almost two years later, researchers revealed that the cognitive impairment can be predicted by a blood test.

Astrocytes are specialised cells abundant in the brain tissue. Just as other members of the glia - resident immune cells of the brain - astrocytes support neuronal cells by supplying them with nutrients and oxygen and protecting them from pathogens. But because glial cells don’t conduct electricity and, at first, didn’t seem to play a direct role in how neurons communicate with one another, their role in health and disease had been overlooked. The latest research from Pittsburgh changes that.

Scientists tested blood samples from participants in three independent studies of cognitively unimpaired elderly people for biomarkers of astrocyte reactivity—glial fibrillary acidic protein, or GFAP—along with the presence of pathological tau. The study showed that only those who were positive for both amyloid and astrocyte reactivity showed evidence of progressively developing tau pathology, indicating predisposition to clinical symptoms of Alzheimer’s disease.

 

  • Bellaver B, Povala G, Ferreira PCL et al. Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease. Nat Med (2023). https://doi.org/10.1038/s41591-023-02380-x

 

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