Baseline NfL and GFAP Biomarker Reference Ranges in Healthy Controls

Researchers have confirmed previous research results demonstrating an association between age and body mass index (BMI) on plasma neurofilament light chain (NfL) levels and have documented new baseline plasma glial fibrillary acidic protein (GFAP) levels by age and BMI in healthy individuals. These results were presented at the Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum 2023, and such reference ranges will be useful in future research as well as in predictive modeling.

As part of this study, a heterogenous group of healthy individuals (16-86 y, White [78.6%], Hispanic [11.7%], Black [8.3%], Asian [4.8%], Native American [0.7%], and Other [1.4%]; n=145) with no evidence of neurologic disease, cancer, traumatic brain injury, and diabetes was enlisted, and plasma NfL and GFAP levels were measured from each using the SR-X Simoa Quanterix platform. Researchers estimated changes in biomarker levels by year of age and generated log-linear predictive models.

Both geometric mean NfL and GFAP levels increased with each year of age:

NfL concentrations: ranging from 2.48 pg/mL (95% CI: 1.87--3.29) at 15-19 years to 7.25 pg/mL (95% CI: 6.10--8.61) at 50-59 years, to 19.55 pg/mL (95% CI: 9.56--39.99) at 80-85 years.  

GFAP levels: increasing from 49.99 pg/mL (95% CI: 41.74--59.87) at 15-19 years to 70.71 pg/mL (95% CI: 59.14--84.54) at 50-59 years, to 121.77 pg/mL (95% CI: 91.07--62.82) at 80-85 years

Models show that expected NfL values increase by 2.78% per year of age (95% CI: 2.39%--3.17%; P<.0001) and expected GFAP levels increase by 1.53% per year of age (95% CI: 1.16%--1.90%; P<.0001). An increase of 1 year of age, adjusted for BMI, increases expected NfL levels by an estimate of 2.97% (95% CI: 2.87%--3.38%; P<.0001) and expected GFAP levels by an estimate of 1.68% (95% CI: 1.29%--2.07%; P<.0001).  An increase of one unit of BMI, adjusted for age, decreased expected NfL levels by an estimate of 1.65% (95% CI: 0.41%--2.87%; P=.0096) and expected GFAP levels by an estimate of 1.44% (95% CI: 0.24%--2.63%; P=.0196).