A recent study published in the Proceedings of the National Academy of Sciences has compared two leading blood tests for detecting Alzheimer’s disease, focusing on their ability to identify brain pathology linked to the condition. The research evaluated total and brain-derived phosphorylated tau-217 (pTau217) in classifying amyloid and tau pathologies associated with Alzheimer’s.
Blood-based biomarkers are becoming more important in diagnosing and predicting Alzheimer’s disease because they are accessible, non-invasive, accurate, and cost-effective. Among these markers, pTau217 is considered one of the most promising due to its strong association with Alzheimer’s-related changes in the brain.
However, a challenge remains regarding the specificity of plasma pTau217 when detecting pathology that originates from the brain. The central nervous system (CNS) and peripheral nervous system (PNS) produce different forms of tau protein. Most current tests measure total pTau217 without distinguishing between these forms, which can reduce accuracy if peripheral tau is present due to other conditions.
To address this issue, researchers compared two assays: the Simoa ALZpath total p-Tau217 assay and the NULISAqpcr BD-pTau217 assay. Both use antibodies specific for pTau217 but differ in how they detect it; only the NULISAqpcr assay specifically targets brain-derived tau.
The study involved two independent cohorts from Hong Kong—one for discovery and another for validation—with participants recruited from both community settings and memory clinics. Participants were grouped based on amyloid PET imaging results into low/no Aβ, intermediate Aβ, or high Aβ categories.
The researchers found that measurements from both assays were strongly correlated across cohorts. Previous studies have shown that chronic kidney disease can raise plasma pTau217 levels regardless of underlying Alzheimer’s pathology because of impaired clearance or altered metabolism outside the brain. In this study, reduced kidney function was linked to higher total pTau217 but had little effect on brain-derived pTau217 measurements.
Both types of pTau217 were elevated in individuals with intermediate or high amyloid burden. Brain-derived pTau217 showed a greater increase than total pTau217 among those with higher amyloid levels. Analyses also indicated that brain-derived pTau217 performed better at distinguishing between people with significant amyloid accumulation versus those without it.
Further analysis using tau PET imaging revealed that both markers increased as tau burden grew but that brain-derived pTau217 generally outperformed total pTau217 in identifying individuals with positive tau findings. The researchers established reference cutoffs for interpreting test results: values above 0.66 pg/mL would be considered positive for Alzheimer’s-related pathology; below 0.36 pg/mL would be negative; intermediate values would require further testing.
According to the authors: “The findings show that brain-derived pTau217 is less susceptible to peripheral changes, including kidney dysfunction, and demonstrates numerically higher diagnostic performance for classifying AD-related brain pathology compared with total pTau217 in several analyses, while both assays show strong overall accuracy.”
They conclude: “Overall, these results highlight brain-derived pTau217 as a highly promising blood-based biomarker for AD, with significant potential for early detection, disease staging, and patient management.”
