Background and Objectives: Plasma phosphorylated tau 217 (p-tau217) has shown strong potential as a blood-based biomarker for detecting amyloid pathology in Alzheimer’s disease. This study evaluated the diagnostic and prognostic utility of plasma biomarkers, including p-tau217, in participants from the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) cohort. Methods: We analyzed paired plasma and CSF samples from 172 J-ADNI participants. CSF and plasma biomarkers were quantified using the LUMIPULSE platform, and the same plasma samples were analyzed using the Simoa platform. The diagnostic accuracy for detecting amyloid pathology and the prognostic value of plasma p-tau217 biomarkers were assessed. Associations between plasma p-tau217 and polygenic risk scores (PRS), as well as potential confounding factors, were examined. Results: Plasma p-tau217 levels measured using Lumipulse and Simoa assays were highly correlated (p < 0.001). All plasma p-tau217 assays showed high diagnostic accuracy for CSF Aβ42/Aβ40-defined amyloid pathology (AUC = 0.98). A single cutoff point based on the Youden index for p-tau217 and p-tau217/Aβ42 achieved >90% specificity and >90% sensitivity. The predefined FDA-approved two-cutoff model for p-tau217/Aβ42 was applicable to this cohort. PRS was significantly associated with plasma p-tau217 independently of APOE genotypes. Subjects with higher plasma p-tau217 levels showed a significantly increased risk of conversion to dementia and larger longitudinal cognitive declines. Plasma p-tau217 levels were significantly influenced by the body mass index, estimated glomerular filtration rate, and high-density lipoprotein cholesterol. Conclusions: Plasma p-tau217 and p-tau217/Aβ42 are robust biomarkers for AD diagnosis and prognosis in the Japanese population.
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. 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. 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
BACKGROUND:Prostaglandin E-major urinary metabolite (PGE-MUM) is an emerging noninvasive biomarker used to evaluate clinical and endoscopic activity in patients with inflammatory bowel disease. Previous studies have shown that PGE-MUM values correlate with colonic inflammation in pediatric ulcerative colitis; however, reference values for children without inflammation have not been defined yet. This study aimed to determine the normal reference values of PGE-MUM in healthy pediatric subjects without inflammatory conditions. METHODS:Between December 2018 and January 2022, we prospectively enrolled 221 participants (cross-sectional study, aged 0-15 years) who were undergoing growth hormone stimulation testing for diagnostic purposes and exhibited no symptoms of inflammation or elevated C-reactive protein levels at a single pediatric center in Japan. PGE-MUM values were measured using a chemiluminescent enzyme immunoassay and assessed for age- and sex-related differences. RESULTS:A total of 218 participants were included in the analysis. Based on age, the participants were classified as young children (2-6 years, n = 147) and older children (7-14 years, n = 66); the reference ranges for the two groups were identified as 18.4-58.7 μg/g·Cr and 12.4-50.3 μg/g·Cr, respectively. The PGE-MUM values tended to decrease with increasing age; however, no significant sex-related differences were observed (median 29.1 μg/g·Cr for boys versus 30.4 μg/g·Cr for girls). CONCLUSIONS:Healthy pediatric subjects generally have higher PGE-MUM values than healthy adults, with particularly elevated values in young children (2-6 years). These observations suggest that age-related variability must be taken into account when using PGE-MUM as a biomarker in young children with ulcerative colitis.
Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials® (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3], was assessed through an interlaboratory study. The following SRMs were assessed: (1) SRM 2969 Vitamin D Metabolites in Frozen Human Serum (Total 25-Hydroxyvitamin D Low Level), (2) SRM 2970 Vitamin D Metabolites in Frozen Human Serum (25-Hydroxyvitamin D2 High Level), and (3) SRM 1949 Frozen Human Prenatal Serum. These SRMs represent three clinically relevant situations including (1) low levels of total 25(OH)D, (2) high level of 25(OH)D2, and (3) 25(OH)D levels in nonpregnant women and women during each of the three trimesters of pregnancy with changing concentrations of vitamin D-binding protein (VDBP). Twelve laboratories using 17 different ligand binding assays and eight laboratories using nine commercial and custom liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays provided results in this study. Commutability of the SRMs with patient samples was assessed using the Clinical and Laboratory Standards Institute (CLSI) approach based on 95
This study presents a retrospective assessment of the diagnostic performance of the newly developed hepatitis B core-related antigen rapid diagnostic test (HBcrAg-RDT) in detecting plasma samples with elevated hepatitis B virus (HBV) DNA levels (≥200,000 IU/ml) in Yaoundé, Cameroon. Samples were collected consecutively from treatment-naïve adults living with HBV between January 1, 2021, and June 30, 2023. Analyzing 146 samples from participants with a median age of 36 years, the HBcrAg-RDT exhibited a sensitivity of 97.5% (95% CI: 86.8-99.9) and a specificity of 77.4% (68.2-84.9) when compared to real-time PCR as the reference standard. These findings suggest that HBcrAg-RDT holds promise as a valuable point-of-care tool for diagnosing high HBV DNA levels, particularly in resource-limited settings. Further research will refine its practicality and effectiveness.
