TOPLINE

Plasma phosphorylated tau 217 (p-tau217) levels decreased within 3 months of lecanemab initiation in patients with Alzheimer's disease (AD), with a more pronounced decline occurring between 3 and 6 months. Patients who experienced greater reductions in p-tau217 showed more favorable cognitive trajectories.

METHODOLOGY

• Researchers conducted a prospective real-world study of 153 patients with early AD (mild cognitive impairment due to AD and mild AD dementia) or subjective cognitive decline, with confirmed amyloid pathology, who initiated lecanemab treatment at a tertiary referral memory clinic in Seoul, South Korea.
• Lecanemab was administered intravenously at 10 mg/kg every 2 weeks, following regulatory guidance and clinical practice recommendations.
• Plasma p-tau217 levels were measured at baseline, 3 months, and 6 months, with additional assessments planned at 12 and 18 months; cognitive performance was evaluated using the Korean version of the Mini-Mental State Examination, Second Edition (MMSE) and CDR-SB at baseline, 3, 6, and 12 months.
• Among the 153 patients, 81 had plasma samples available at baseline, 3 months, and 6 months and were included in trajectory pattern analysis.
• Longitudinal changes in plasma p-tau217 were assessed, and trajectory patterns were identified.

TAKEAWAY

• Plasma p-tau217 levels decreased significantly at 3 months compared with baseline (P = .011), with a more pronounced decline at 6 months (P < .001) and sustained reduction and slight progression at 12 months (P < .001).
• Two distinct trajectory groups were identified: the greater reduction group (n = 29) showed a consistent and marked decrease in p-tau217 from baseline to 6 months, whereas the lesser reduction group (n = 52) exhibited smaller changes with a transient increase or minimal decrease at 3 months and a modest reduction at 6 months.
• Hypertension was independently associated with a lower likelihood of belonging to the greater reduction group (odds ratio, 0.09; P = .003); in slope-based analysis, hypertension was associated with a slower decline in p-tau217 levels (beta, 0.039; P = .014).
• Patients in the greater reduction group had higher baseline MMSE scores than the lesser reduction group (24.7 vs 22.7; P = .016). Those in the greater reduction group exhibited more favorable cognitive trajectories, with MMSE scores remaining stable or improving slightly and CDR-SB scores increasing more slowly compared with that in the lesser reduction group (P = .023 and P < .001, respectively).

IN PRACTICE

"Early changes in plasma p-tau217 may help identify responders and non-responders, enabling more individualized treatment strategies," the authors of the study wrote. "These findings support the clinical utility of plasma p-tau217 as a dynamic biomarker of treatment response and may contribute to the development of biomarker-guided, individualized therapeutic strategies in real-world practice," they added.

SOURCE

The study was led by Sung Hoon Kang, Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine in Seoul, South Korea. It was published online on July 31 in Alzheimer's & Dementia.

LIMITATIONS

This single-center study had a modest sample size, particularly for subgroup analyses, and a relatively short cognitive follow-up duration. Direct measures of tau buildup, such as tau PET scans or plasma/cerebrospinal fluid microtubule binding region–tau243 measurements, were not available, precluding direct evaluation of underlying tau burden's contribution to differential p-tau217 response.

DISCLOSURES

The study was supported by grants from the National Research Foundation of Korea funded by the Korea government, Korea University Guro Hospital and Korea University Medicine, the Starting Growth Technological R&D Program funded by the Ministry of SMEs and Startups, Korea, and the Seoul R&BD Program through the Seoul Business Agency funded by the Seoul Metropolitan Government. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.