Age specific reference intervals for plasma biomarkers of neurodegeneration and neurotrauma in a Canadian population

•Normative concentrations of Aβ42/40, p-tau-181, NfL and GFAP change with age.•They had U-shaped curves, decreasing in pediatrics and increasing in late adulthood•Age specific reference intervals can improve interpretation of biomarkers results. In this study, we aimed to create reference intervals (RI) using a large Canadian population-based cohort, for plasma protein biomarkers with potential utility to screen, diagnosis, prognosticate and manage a variety of neurological diseases and disorders. RIs were generated for: the ratio of amyloid beta 42 over 40 (Aβ42/40), phosphorylated tau-181 (p-tau-181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). 900 plasma specimens from male and female participants aged 3–79 years old were obtained from the Statistics Canada Biobank, which holds specimens from the Canadian Health Measures Survey. Analysis of Aβ42/40, p-tau-181, NfL and GFAP was performed on the Quanterix Simoa HD-X analyzer using the Neurology 4-plex E and p-tau-181 assays. Discrete RIs were produced according to Clinical Laboratory Standards Institute guidelines (EP28-A3c). Continuous RIs were created using quantile regression. For discrete RIs, significant age partitions were determined for each biomarker. No significant sex partitions were found. The following ranges and age partitions were determined: Aβ42/40: 3–