CSF and Blood Neuronal Injury Biomarkers in Spinal Bulbar Muscular Atrophy and Amyotrophic Lateral Sclerosis 4
Pashtun-Poh Shahim1, Abdullah Alqahtani1, Angela Kokkinis1, Narjis Kazmi1, Marie Ezuma-Ngwu1, Jahan Misra1, George Harmison1, Elizabeth Howe1, Alice Schindler1, Christopher Grunseich1
1National Institutes of Health
Objective:

Evaluate whether neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and Total-tau (T-tau) are altered in two neuromuscular diseases.

 

Background:

Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis 4 (ALS4) are two forms of motor neuron disease characterized by slow disease progression.

 

Design/Methods:

Thirty adult participants (10 SBMA, 8 ALS4, and 12 controls) were enrolled in natural history studies at the National Institutes of Health and underwent paired CSF and serum sampling.

 

Results:

CSF NfL, GFAP, and T-tau correlated with corresponding levels in serum (r=0.47, r=0.74, and r=0.70, respectively). Patients with SBMA had increased concentrations of CSF NfL (median, 719 pg/mL) as compared to ALS4 (median, 296 pg/mL; p=0.034) or controls (median, 395 pg/mL; p=0.024). CSF GFAP was increased in patients with SBMA (median, 8840pg/mL) as compared to controls (median, 5315 pg/mL; p=0.029) but not compared to ALS4 (median, 5015 pg/mL; p=0.31). In contrast, serum concentrations of either biomarkers did not differ between SBMA, ALS4, or controls. Longitudinal changes in CSF NfL and GFAP were associated with changes in SBMA Functional Rating Scale (r=–0.42 and r=–0.48, respectively). Also, changes in CSF NfL and GFAP were associated with changes in TUG, total adult myopathy assessment tool, and 6-minute walk test. Over the course of 24 months, the average change in ALSFRS was 0.83 points, while the changes in CSF NfL and GFAP were progressive (increased 1.3 fold and 1.4 fold, respectively).

Conclusions:
The results suggest that SBMA patients have increased concentrations of CSF NfL and GFAP as compared to ALS4 and controls, and higher levels of these biomarkers are associated with disease severity. Importantly, these results indicate that SBMA is associated with progressive neurodegeneration and that either CSF NfL or GFAP may be useful for patient stratification and monitoring treatment effects in trials of disease-modifying therapies.
10.1212/WNL.0000000000211561
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