Establishing Demographic and Comorbidity Based Reference Ranges for NfL and GFAP in Healthy Controls
Tyler Borko1, Britney Barrera1, Alanna Ritchie1, Sean Selva1, Stefan Sillau1, Eric Engebretson1, Rebecca Seale1, Brooke Valdez1, Enrique Alvarez1, John Corboy1, Anna Shah1, Robert Gross1, Diego Silva3, Gregory Owens1, Amanda Piquet1, Jeffrey Bennett1, Timothy Vollmer1, Salim Chahin4, Kavita Nair2
1Neurology, 2Neurology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz School of Medicine, 3Bristol-Myers Squibb, 4Neurology, Washington University in St. Louis School of Medicine
Objective:

To assess the effect of sex and age on plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels in a healthy control (HC) cohort.

Background:

Blood NfL levels vary with age and comorbid disorders. The effect of age on blood GFAP has not been investigated.

Design/Methods:

HC subjects without neurologic disease, cancer, diabetes, and traumatic brain injury were recruited from community and wellness events. Plasma NfL and GFAP were measured using the SR-X Simoa Quanterix platform. Changes in biomarker levels per year of age were estimated and log-linear predictive models generated.

Results:

110 of 155 HC samples have been analyzed to date. Age ranges from 16.4 to 59.6 years with the following distribution: 15-19 (11.82%), 20-30 (36.36%), 30-40 (21.82%), 40-50 (15.45%) and 50-60 (14.55%). Sex and racial distribution were female (64.5%), White (78.2%), 15.5% Hispanic, 7.4% Black, 5.5% Asian, 0.9 % American Indian, 1.8 % other. Geometric mean NfL concentrations increased by age, ranging from 2.47 pg/ml (CI: (1.87, 3.29) at 15-19 years to 7.22 pg/ml (CI: (5.97, 8.73) at 50-60 years. Geometric mean GFAP values increased from 49.99 pg/ml (CI: (41.74, 59.87) at 15-19 years to 72.56 pg/ml (CI: (60.16, 87.51) at 50-60 years. Adjusting for age and gender, expected NfL values increased by 2.57% per year (95% CI: (1.90%, 3.25%), p < 0.0001) overall, 2.72% (95% CI:(1.96%, 3.49%), p < 0.0001) in females, and 2.22% (95% CI:  (0.87%, 3.58%), p = 0.0018) in males.  Expected GFAP increased by 0.94% per year (95% CI:  (0.26%, 1.62%), p = 0.0067) overall and by 0.95% (95% CI:  (0.11%, 1.80%), p = 0.0273) in females.

Conclusions:

Utilizing more stringent criteria for HC, our study replicates recent reports on blood NfL levels using national cohorts and provides novel data of plasma GFAP levels across a broad age distribution.

10.1212/WNL.0000000000203928