A combination of two plasma biomarkers may help identify established Alzheimer’s disease and signal faster cognitive decline among patients with amyloid pathology, according to a prospective cohort study published in The Lancet Neurology.
Researchers evaluated whether adding the blood biomarker eMTBR-tau243 to plasma p-tau217 could improve identification of patients with tau pathology and Alzheimer’s disease–related cognitive impairment. Plasma p-tau217 reflects amyloid-related disease processes, while eMTBR-tau243 reflects tau neurofibrillary tangles—one of the defining pathological features of Alzheimer’s disease.
The study included 572 patients with cognitive symptoms, including subjective cognitive decline, mild cognitive impairment, or dementia, who underwent clinical assessment, imaging, and biomarker testing. Investigators measured plasma p-tau217 and eMTBR-tau243 using mass spectrometry–based assays and compared results with amyloid and tau positron emission tomography (PET), cerebrospinal fluid (CSF) biomarkers, and cognitive measures.
Among patients who were positive for plasma p-tau217, the addition of eMTBR-tau243 improved identification of those with established Alzheimer’s disease, defined by both amyloid and tau biomarker positivity along with clinical symptoms. In this group, the combined biomarker approach showed 81% accuracy and an 84% positive predictive value for established disease.
The biomarker combination also helped distinguish patients with higher tau burden on PET imaging from those with lower levels of pathology. Among patients with positive p-tau217 results, eMTBR-tau243 demonstrated 87% accuracy in identifying those with high tau pathology.
Elevated eMTBR-tau243 levels were associated with greater tau accumulation and worse cognitive performance at baseline, as well as faster cognitive decline over time. Patients with higher levels of this biomarker showed greater increases in tau PET signal and more rapid worsening on cognitive tests during follow-up.
The findings support a two-step testing strategy in which plasma p-tau217 is used to detect amyloid pathology, followed by eMTBR-tau243 to assess whether tau pathology is contributing to symptoms. This approach may help distinguish patients with asymptomatic amyloid pathology from those with clinically significant Alzheimer’s disease.
Researchers noted that combining biomarkers linked to different stages of Alzheimer’s pathology may improve diagnostic precision and help stratify patients in clinical and research settings. The approach could also help identify patients with higher tau burden, which may be relevant when considering therapies targeting amyloid or tau.
The study population was drawn primarily from secondary memory clinics in Sweden, with validation in an independent US cohort. The researchers noted that additional studies in broader clinical settings are needed to confirm generalizability.
The study funders had no role in study design, data collection, data analysis, data interpretation, or the decision to publish. Several researchers reported relationships with pharmaceutical and diagnostic companies.
Source: The Lancet Neurology
