PLASMA tau biomarkers, particularly phosphorylated tau217 and its ratio to non-phosphorylated tau, demonstrated strong associations with cognitive performance in a study involving 123 participants who underwent post-mortem assessment for Alzheimer’s disease pathology.
The findings highlighted the potential of blood-based biomarkers to reflect clinical features of Alzheimer’s disease and support future symptom monitoring.
Researchers investigated associations between phosphorylated and non-phosphorylated tau species measured in blood samples collected during life and neuropsychological outcomes in participants with subsequent brain donation.
The cross-sectional study included 123 participants from the Boston University Alzheimer’s Disease Research Center who underwent neuropsychological testing during life and neuropathological assessment following death.
Alzheimer’s disease pathology was evaluated using National Institute on Aging–Reagan criteria.
The mean age at blood collection was 78.17 years (standard deviation: 8.55), while 55 participants (44.7%) were female.
Researchers used immunoprecipitation mass spectrometry to measure six phosphorylated tau species, including p-tau181, p-tau199, p-tau202, p-tau205, p-tau217 and p-tau231.
Two non-phosphorylated tau peptides and their corresponding phosphorylated tau ratios were also evaluated to determine associations with cognitive performance.
The p-tau217/tau212–221 ratio demonstrated the strongest associations with neuropsychological outcomes, followed closely by plasma p-tau217.
Both biomarkers were significantly associated with six of the eight neuropsychological measures assessed (p<0.05).
Regression coefficients for the p-tau217/tau212–221 ratio ranged from −0.564–0.404, compared with −0.478–0.377 for p-tau217.
Other biomarkers, including the p-tau205/tau195–209 ratio, p-tau205 and p-tau231, demonstrated weaker or less consistently significant associations.
Notably, the effect sizes observed for the p-tau217 ratio and p-tau217 were similar to those associated with autopsy-confirmed Alzheimer’s disease (regression coefficients: −0.564–0.393).
These findings suggested that selected plasma tau measurements may capture clinically relevant differences in cognitive performance associated with Alzheimer’s pathology.
The researchers concluded that plasma p-tau217 and selected tau ratios showed promising associations with clinical outcomes in Alzheimer’s disease.
However, several methodological considerations limit immediate clinical application.
Individual neuropsychological analyses included between 65 and 91 participants, while the interval between the final clinical assessment and autopsy ranged from 0–12 years, with a mean of 5.54 years.
Furthermore, the cross-sectional design did not establish whether changes in plasma tau biomarkers reliably reflect cognitive deterioration over time.
Additional longitudinal studies are therefore needed to determine their value for tracking symptoms and informing clinical management.
Overall, the findings identified plasma p-tau217 and the p-tau217/tau212–221 ratio as promising candidates for future Alzheimer’s disease monitoring, while reinforcing the need for further clinical validation.
Reference
Labonte J et al. Leveraging immunoprecipitation mass spectrometry and neuropathology to identify the clinical value of different blood tau species in Alzheimer’s disease. J Neuro. 2026
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