New Study Uncovers the Link Between Activated Microglia and Neurofilament Light in Multiple Sclerosis

A recently published study of patients with multiple sclerosis (MS) distinguished a relationship between increased brain innate immune cell activation and serum neurofilament light (sNfL) in this patient populace. Most importantly, the findings emphasize the connection between MS and neuronal damage and microglial activation, as well as the contribution of rim-active lesions to neuronal damage.

Led by Maija Saraste, Ph.D., Department of Neurology, University of Turku, the preliminary expected to assess the relationship between serum NfL and translocator protein (TSPO)- PET-measurable microglial activation in patients with MS. Distribution volume ratio (DVR) was used to measure specific TSPO-binding radioligand [11C]PK11195 binding in a group of 44 MS patients and 24 age- and sex-matched controls, and single molecule assays were used to measure sNfL levels.

Imaging and sampling were separated by an average of 12 days. The MS cohort had a median sNfL level of 19.0 (IQR, 9.1-24.3) pg/mL at baseline. The MS cohort also had a higher level of radioligand binding in the NAWM compared to the white matter of HCs (1.20 vs 1.18, P =.026) and [11C]PK11195-binding in the whole brain (1.20 vs 1.18, P =.015) than the HC cohort. DVR values in the brain were correlated with DVR values in the rim lesion, perilesional NAWM, and normal-appearing white matter (NAWM) (r = 0.75, P.001).

There was a correlation between increased [11C]PK11195-DVR in NAWM (r = 0.48, P =.036), perilesional NAWM (r = 0.58, P = 0.009), at the lesion rim (r = 0.59, P = 0.008), and T1 hypointensive lesions (r = 0.49, P = 0.034) in individuals with high brain (DVR). Of note, all relationships, aside from T1 DVR, were sustained in partial age-correlated correction analyses.

Higher DVR in the lesion rim (estimate, 0.49, 95% CI, 0.15-0.83, P [FDR] = 0.04) and higher perilesional NAWM (estimate, 0.48, 95% CI, 0.14-0.83, P [FDR] = 0.04) were found to be linked to higher levels of sNfL in an FDR-corrected univariate linear regression model. Additionally, these observations were associated with a larger volume of rim-active lesions (estimate, 0.50, 95% CI, 0.17-0.84, P [FDR] = 0.04) and a higher number of rim-active and overall-active lesions (estimate, 0.46 [95% CI, 0.10-0.81] P [FDR] = 0.4, estimate, 0.47 [95% CI, 0.12-0.82, P [FDR] = 0.04). [11C]PK11195-DVR at the lesion rim accounted for 35% of the variance in sNfL, and an increased sNfL was associated with a larger T1 lesion load. The volume of rim-active lesions accounted for 37% of the variance in sNfL.

“The strongest associations were observed between microglial activation at the rim of chronic T1 hypointense lesions and in the perilesional NAWM and sNfL. NfL is now considered the most promising biomarker candidate for nervous system damage-related pathology in MS,” Saraste et al wrote. “Most pronounced changes in NfL levels are seen in association with focal inflammatory lesion-induced axonal damage.”

They added, “More modest, but significant alterations are seen in the context of smoldering disease and MS disease progression.” Our study cohort had no concurrent gadolinium-enhancing lesions or recent relapses. Hence, the increases in sNfL concentration observed in this cohort are most likely associated with the smoldering disease process.”

While taking a gander at the particular relationship among sNfL and different lesion subtypes, results showed that expanded levels connected with a bigger proportion of lesions containing activated microglia and a smaller proportion of inactive lesions (ρ = 0.64, p = 0.003 and ρ = – 0.64, p = 0.003, respectively). Agents likewise noticed relationships between sNfL and both the number and volume of lesions containing activated microglia (ρ = 0.6, p = 0.006 and ρ = 0.57, p = 0.012, respectively), while there was no correlation between sNfL and the number or volume of inactive lesions (ρ = 0.12, p = 0.63 and ρ = −0.028, p = 0.91).