Neurofilament light tied to inflammation, but not cognitive decline, in AD

Plasma levels of neurofilament light (NFL) correlate strongly with the tumour necrosis factor-alpha receptor (TNF-R1), and may act as a biomarker for peripheral inflammation in Alzheimer’s disease (AD), a recent study has found. However, NFL does not seem to signal cognitive decline.

The study included 40 AD patients (mean age 78±8 years, 25 percent men) who underwent specific clinical evaluation and medical record reviews. At baseline and at the 1- and 2-year follow-up, plasma biomarkers were measured using appropriate assays. Cognitive decline was evaluated using the Mini-Mental State Examination (MMSE).

The baseline mean concentration of TNF-R1 was 2.8±1.4×10³ pg/mL, which grew significantly to 3.3±1.4×10³ pg/mL at 1 year (p=0.018) and to 4.1±2.0×10³ pg/mL at 2 years (p<0.0001). Meanwhile, levels of TNF-alpha dropped over the 2-year follow-up period (p<0.0001). Similar patterns of effect were reported for interleukin-6, which decreased significantly over time, and its receptor, which increased progressively.

In comparison, NFL showed no change from baseline to 1 year, but increased significantly by 2 years (p=0.0052).

The researchers found a significant correlation between NFL and TNF-R1 both at 1 year (rho, 0.41; p=0.0122) and 2 years (rho, 0.69; p<0.0001). Moreover, the changes in NFL and TNF-R1 concentrations from the first and second follow-ups were also linked (p=0.005). NFL was also associated with TNF-alpha at baseline (rho, 0.33; p=0.0433) and at 2 years (rho, 0.36; p=0.0277).

In contrast, NFL showed no interaction with MMSE score at baseline, but achieved significant correlation at 2 years (p=0.006). Changes in cognitive scores over time were not associated with NFL kinetics.

“[T]hese data suggest that, although the level of inflammation biomarkers in the blood may vary over time, their profile appears to have limited informative value on cognitive decline in patients with AD,” the researchers said.

“However, the results need to be confirmed, particularly because of the limited number of patients in each group,” they added.