Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by changes involving amyloid-beta and tau proteins in the brain. Lecanemab is an anti-amyloid therapy approved for people with early AD that has been shown to slow disease progression. However, treatment responses can vary between individuals, creating a need for accessible ways to monitor biological changes during therapy.
Researchers from Korea University College of Medicine, led by Associate Professor Sung Hoon Kang, investigated whether changes in plasma phosphorylated tau 217 (p-tau217), a blood-based biomarker associated with Alzheimer's disease pathology, could serve as an early marker of response to lecanemab. The prospective real-world study followed 153 patients receiving lecanemab. This paper was made available online on July 31, 2026, and was published in Volume 22, Issue 8 of the journal Alzheimer's & Dementia in August 01, 2026.
The researchers measured plasma p-tau217 at baseline and during treatment and assessed cognitive measures, including the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating–Sum of Boxes (CDR-SB). Of the 153 patients, 81 had complete p-tau217 measurements at baseline, 3 months, and 6 months and were included in the analysis of distinct biomarker response patterns. Cognitive assessments were followed for 12 months.
Dr. Kang explains, "We found that plasma p-tau217 levels decreased significantly from 3 months after treatment initiation. The greatest decline occurred between 3 and 6 months, followed by a plateau." Patients showed two distinct p-tau217 response patterns. Those with greater reductions in p-tau217 had more favorable cognitive trajectories, particularly slower worsening of CDR-SB scores.
The researchers also found that baseline hypertension was independently associated with a weaker p-tau217 response. The greater-reduction group included 29 patients, compared with 52 in the lesser-reduction group. Hypertension was present in 10.3% of patients in the greater-reduction group and 42.3% of those in the lesser-reduction group.
Importantly, the association between p-tau217 trajectories and cognitive outcomes remained significant after accounting for baseline clinical and biomarker characteristics. The greater-reduction group showed more favorable MMSE trajectories, while CDR-SB scores increased more slowly than in the lesser-reduction group. The difference in CDR-SB trajectories between groups was statistically significant (p < 0.001).
Dr. Kang notes, "As blood-based Alzheimer's biomarkers become widely available, repeated p-tau217 testing may allow clinicians to monitor biological treatment response in a manner that is less invasive, less costly, and more accessible than repeated PET imaging."
The findings suggest that repeated p-tau217 measurements could provide information about biological changes during lecanemab treatment and may help identify differences in treatment response. However, larger, multicenter studies with longer follow-up are needed to validate these response patterns and establish clinically meaningful thresholds.
Ultimately, the study highlights the potential of plasma p-tau217 as an accessible, minimally invasive biomarker for monitoring biological response to lecanemab. Future research will need to determine whether repeated p-tau217 measurements can be incorporated into routine clinical care and whether biomarker-guided monitoring can improve treatment decisions and patient outcomes.
