Biomarker Test May Detect Alzheimer's Pathology Earlier: Study Finds - Video

Years before tau tangles show up in brain scans of patients with Alzheimer's disease, a biomarker test developed at the University of Pittsburgh School of Medicine can detect small amounts of the clumping-prone tau protein and its misfolded pathological forms that litter the brain, cerebrospinal fluid and potentially blood, new research published in Nature Medicine suggests.

The cerebrospinal fluid biomarker test correlates with the severity of

cognitive decline, independent of other factors, including brain amyloid deposition, thereby opening doors for early-stage disease diagnosis and intervention.

The clumping of tau protein into well-ordered structures referred to by pathologists as "neurofibrillary tangles" is a more defining event for Alzheimer's disease as it is more strongly associated with the cognitive changes seen in affected people.

In this latest research, using the tools of biochemistry and molecular biology, researchers identified a core region of the tau protein that is necessary for neurofibrillary tangle formation. Detecting sites within that core region of 111 amino acids, a sequence they call tau258-368, can identify clumping-prone tau proteins and help initiate further diagnostics and early treatment. In particular, the two new phosphorylation sites, p-tau-262 and p-tau-356, can accurately inform the status of early-stage tau aggregation that, with an appropriate intervention, could potentially be reversed.

Reference: Islam, T., Hill, E., Abrahamson, E.E. et al. Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease. Nat Med (2025). https://doi.org/10.1038/s41591-024-03400-0