Blood Test Measures Amyloid Seeding Activity to Detect Alzheimer’s Disease

Confirmation typically relies on cerebrospinal fluid testing (CSF) or positron emission tomography (PET), approaches that may be invasive, costly, or limited in availability. Although blood biomarkers are advancing rapidly, few directly measure amyloid beta (Aβ) aggregation seeding activity, a core process in AD pathology. Addressing this gap, a new study shows that plasma Aβ seeding activity measured with an ultrasonic amplification assay can accurately identify AD and mild cognitive impairment (MCI) due to AD.

Researchers at Xuanwu Hospital of Capital Medical University (Beijing, China) developed a blood-based diagnostic method using real-time ultrasonic protein misfolding cyclic amplification (PMCA) to detect plasma Aβ aggregation seeding activity. The findings were published online in the Chinese Medical Journal on June 16, 2026. In a two-stage study, the assay accurately identified AD and MCI due to AD, with diagnostic accuracy exceeding 90% in the validation cohort.

The method integrates ultrasonic and fluorescence techniques to track Aβ aggregation kinetics in real time and completes detection within 24 hours. It was applied for the first time to measure plasma Aβ seeding activity and, according to the team, can detect Aβ oligomers at concentrations as low as 1 femtomole. The authors attribute its sensitivity and speed to ultrasonic cavitation, where energy at spherical interfaces promotes fibril formation, and localized heat and shear induce misfolding, markedly increasing amplification efficiency.

The study used a rigorous two-stage design. A discovery phase enrolled 120 participants to establish preliminary diagnostic efficacy. An independent validation phase included 429 participants comprising cognitively normal individuals, patients with MCI due to AD, patients with AD, and patients with non-AD dementias; immunodepletion experiments confirmed that the measured signal was specifically induced by Aβ seeds in plasma.

In the validation cohort, plasma Aβ seeding activity was significantly higher in AD than in cognitively normal individuals and in non-AD dementia (P < 0.001). Individuals with MCI due to AD also showed elevated seeding activity, supporting earlier-stage identification. Receiver operating characteristic (ROC) analyses yielded areas under the curve (AUCs) of 0.93 (AD vs. cognitively normal), 0.91 (AD vs. non-AD dementia), 0.92 (MCI due to AD vs. cognitively normal), and 0.90 (MCI due to AD vs. non-AD dementia).

According to the authors, the minimally invasive assay could support large-scale community and primary care screening, differentiation of AD from other dementias, assessment of disease severity, and monitoring of progression. They also note potential use as an objective biomarker for participant selection and efficacy evaluation in clinical trials, and plan larger-scale validation with long-term follow-up to evaluate prediction of disease course.

“The most important significance of this study lies in providing clinicians with a minimally invasive, efficient, and accurate AD diagnostic tool,” said Prof. Jianping Jia of Xuanwu Hospital of Capital Medical University.