Prospective study on clinical utility of plasma p-Tau217 and other biomarkers in Japanese memory clinics using the LUMIPULSE platform

Background In recent years, plasma levels of phosphorylated tau species, particularly p-tau217, have emerged as reliable indicators of amyloid-β (Aβ) pathology in the brain. However, real-world data on plasma biomarkers across diverse populations remain limited. We conducted a prospective multicenter study under real-world clinical settings to evaluate diagnostic performance of plasma biomarkers, including p-tau217, in discriminating amyloid status among a Japanese population. Methods A total of 332 participants were recruited from seven memory clinics across Japan. Participants were categorized into four clinical subgroups: cognitively unimpaired (CU), mild cognitive impairment (MCI), Alzheimer’s disease dementia (ADD), and non-ADD. We measured Aβ40, Aβ42, p-tau181, total-tau, and neurofilament light chain (NfL) in CSF and Aβ40, Aβ42, p-tau217, p-tau181, glial fibrillary acidic protein (GFAP) and NfL in plasma using the LUMIPULSE platform. Amyloid status was determined by amyloid PET imaging and/or CSF Aβ42/40 ratio. Results Significant differences were observed in plasma biomarker levels, including Aβ42/40, p-tau217, p-tau181, GFAP, and NfL across clinical categories. Plasma p-tau217 and p-tau217/Aβ42 achieved high diagnostic accuracy, with areas under the curve (AUC) exceeding 0.9 with PET amyloid status as the reference, demonstrating comparable performance to the in vitro diagnostic (IVD)-approved CSF Aβ42/40 ratio. The two-cutoff approach using plasma p-tau217 and p-tau217/Aβ42 to achieve 90% sensitivity and 90% specificity provided high negative and positive predictive values. The intermediate range defined by these two-cutoff points was narrower for p-tau217/Aβ42 than for p-tau217. The predefined U.S. Food and Drug Administration (FDA)-approved two-cutoff points were applicable to this cohort with good accuracy. Concordance of plasma p-tau217 or p-tau217/Aβ42 with PET or CSF Aβ42/40 status ranged from 87% to 93%, although larger discordant results were observed in the non-ADD group. Conclusions This study demonstrates the clinical utility of plasma p-tau217 and p-tau217/Aβ42 ratio for real-world diagnostic evaluations of dementia. However, careful interpretation of plasma biomarker is warranted in cases showing discordant results with PET or CSF findings. Supplementary Information The online version contains supplementary material available at 10.1186/s13195-026-01997-7.