Amyloid beta misfolding predicts Alzheimer's years before symptoms appear

Widely used Alzheimer’s biomarker P-tau 217 reliably detects the disease only at the clinical stage. The protein misfolding of amyloid beta indicates an increased risk years earlier.

The misfolding of the amyloid beta protein is the strongest blood-based predictor for Alzheimer's disease in the asymptomatic stage, indicating the risk of the disease years before it is clinically diagnosed and much earlier than the widely used plasma biomarker P-tau 217. This is the conclusion reached by a study led by Professor Klaus Gerwert (PRODI, Ruhr University Bochum, Germany). The research team analyzed blood samples from 17 years of 779 subjects in the population-based ESTHER cohort of the German Cancer Research Center (DKFZ) to compare the effectiveness of leading blood biomarkers throughout the entire course of Alzheimer's disease. The study was published in the journal EMBO Molecular Medicine on July 16, 2026.

The study compares how well common blood-based biomarkers can predict eventual Alzheimer's dementia in persons without clinical symptoms. To do so, the researchers were able to use blood samples from the ESTHER study, a major long-term study on the health of elderly persons at the DKFZ.

The analysis shows that different biomarkers predominate at different stages of the disease. "P-tau 217 demonstrated outstanding diagnostic effectiveness once the Alzheimer's disease reached the clinical stage," says Gerwert. Its accuracy was comparable to that of established biomarkers like the Aβ42/40 ratio in cerebrospinal fluid (CSF) and amyloid PET imaging. However, the biomarker's predictive power was only moderate in the preclinical, asymptomatic stage (AUC = 0.67). For comparison: Values of about 0.8 or higher are considered highly significant.