A New Biomarker Test Promises Early Alzheimer’s Detection

A breakthrough cerebrospinal biomarker test developed by researchers at the University of Pittsburgh School of Medicine could change the future of Alzheimer’s diagnosis and treatment. This test, published in Nature Medicine, detects tau protein abnormalities in cerebrospinal fluid (CSF) and potentially blood, long before they are visible on brain scans. Tau tangles, which are more closely associated with cognitive decline than amyloid-beta plaques, are a hallmark of Alzheimer’s disease. The new test identifies early-stage tau aggregation, offering a critical window for intervention.

The study, led by Dr. Thomas Karikari, assistant professor of psychiatry, focuses on a 111-amino acid region of the tau protein, known as tau258-368, which plays a key role in tau tangle formation.

The researchers discovered two phosphorylation sites—p-tau-262 and p-tau-356—within this region that serve as reliable indicators of early aggregation. This advancement could allow clinicians to detect Alzheimer’s pathology years before the typical neurofibrillary tangles appear on brain scans, offering up to a decade of lead time for early diagnosis and intervention.

Dr. Karikari emphasizes that early detection is crucial for effective Alzheimer’s treatment. “Patients with minimal deposits are more likely to benefit from new therapies compared to those with significant brain deposits,” he explains. This test provides an opportunity to initiate treatments before substantial cognitive decline occurs, potentially altering the course of the disease.

The new biomarker test marks a significant shift in Alzheimer’s diagnostics, which have traditionally focused on amyloid-beta plaques. While amyloid-beta accumulation is often seen early in Alzheimer’s, not everyone with these plaques develops cognitive symptoms. The test offers a more reliable predictor of Alzheimer’s progression by focusing on a protein more directly linked to the cognitive symptoms of the disease.

This research holds immense potential for Alzheimer’s patients, offering an early, cost-effective method for diagnosing the disease and providing new opportunities for timely interventions that could improve patient outcomes and quality of life.

More Information: Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease, Nature Medicine (2025). DOI: 10.1038/s41591-024-03400-0