Biomarkers

Alzheimers Dement. 2025 Dec;21 Suppl 2:e100166. doi: 10.1002/alz70856_100166.

ABSTRACT

BACKGROUND: ADAPT is a three-stage UK multi-centre study investigating the impact of plasma p-tau217 on AD diagnosis, treatment, and quality of life and health economic outcomes. Stage 1 validated two commercially available plasma p-tau217 assays against CSF AD biomarker status and derived cut-points for clinical interpretation, which were then evaluated in an independent amyloid PET cohort.

METHOD: Patients in the UCL CSF Cohort were classified as CSF AD biomarker positive if CSF Aβ42/Aβ40<=0.065 and p-tau181>57 pg/mL (Lumipulse, Fujirebio). Patients in the Imperial Amyloid PET Cohort attended for clinical amyloid PET scans, categorized positive/negative by visual read. EDTA plasma samples from both cohorts were tested blind at a UKAS accredited clinical laboratory using the Lumipulse G (Fujirebio) and ALZpath Simoa (Quanterix) assays. We derived cut-points for 95% sensitivity and 95% specificity from the CSF cohort, and evaluated the percentage of individuals assigned intermediate plasma p-tau217 results, negative (NPV) and positive predictive value (PPV) of the tests. These cut-points were then applied to the amyloid PET cohort to ascertain the same metrics in relation to amyloid PET status.

RESULT: The CSF cohort (Table 1) comprised 257 individuals (mean age 63.3 years, standard deviation 7.3 years; 60% male, 60% CSF AD biomarker positive, median fold change for Lumipulse 6.8, ALZpath 4.1; Figure 1a and b). For Lumipulse, 95% sensitivity and 95% specificity cut-points were 0.153 and 0.422 pg/ml, with NPV 91% and PPV 96% respectively; 19% of individuals had intermediate values. On applying these cut-points to the amyloid PET cohort (n = 76, mean age 68.3 years, standard deviation 8.6 years; 45% male, 63 amyloid PET positive, median fold change for Lumipulse 3.9, ALZpath 3.2; Figure 1c and d), 34% had intermediate values, with NPV 89% and PPV 91%. For ALZpath, 25% of individuals had intermediate values in the CSF cohort and 30% in the amyloid PET cohort (Table 2).

CONCLUSION: In both cohorts the accuracy of Lumipulse plasma p-tau217 in those assigned either high or low values exceeded 90%, and NPV was greater than for ALZpath p-tau217. The validated Lumipulse cut-points will be implemented as part of a randomized controlled trial of result disclosure in community memory clinics.

PMID:41442261 | DOI:10.1002/alz70856_100166