Dr. Cheryl Wellington, DMCBH member and Professor and Vice-Chair of Research in the Department of Pathology and Laboratory Medicine, and her lab have created UBC’s Neurology Fluid Biomarker Network. The network’s vision is to expand into a distributed core facility for neurology fluid biomarkers to develop, validate and implement tests that improve the diagnosis, prognosis and management of neurological disorders.
Increasing the use of fluid biomarkers will enable early detection of neurodegeneration, improve risk stratification, and increase equitable neurology care for diverse patients (particularly rural and remote) whose access to neuroimaging or invasive neuromonitoring resources may be limited.
Recently, the Wellington lab published two papers that are focused on creating reference intervals (RIs) for blood-based neurology biomarkers.
“Our research will form the basis of improving methods to interpret fluid biomarker results in populations spanning neurotrauma and neurodegeneration,” says Jennifer Cooper, PhD Candidate in the Wellington Laboratory. “In both publications, we have defined normative ranges for biomarkers using large population-based samples, giving us a robust comparison group to use as a benchmark for defining normal and abnormal values in future studies.”
The first publication is led by Research Associate and Director of the Fluid Biomarker Facility Dr. Sophie Stukas, creating reference intervals in the pediatric age range for two biomarkers – serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). The paper was published in Clinical Chemistry and Laboratory Medicine (CCLM).
Establishing normative data is a critical benchmark in the analytical validation process, especially in children, as little is known about how brain development may impact potential biomarkers. The study found NfL and GFAP displayed high levels in infants that decreased during childhood. These normative data are expected to inform future pediatric studies on the importance of age on neurological blood biomarkers.
The second publication led by Jennifer Cooper, used a large Canadian population-based cohort to create reference intervals for ages 3 to 79 for four plasma protein biomarkers – plasma amyloid beta 42/40 (Aβ42/40), phosphorylated tau-181 (p-tau-181), NfL, and GFAP. This paper was published in the Clinical Biochemistry journal.
This study replicated the findings of the first, showing similar trajectories in pediatrics. It then expanded on these findings to show that U-shaped curves occurred across the lifespan with the decrease in young children leading to a plateau during adolescence and early adulthood, followed by increasing levels in older adults. These dynamic changes observed across the lifespan point to the need to take age into account when interpreting these biomarker concentrations.
Collectively, these data indicate that the use of age specific RIs can improve the precision of interpreting neurological plasma biomarker levels, especially in pediatric and older populations where normative biomarker levels can change more rapidly.