Neurofilament light chain and Alzheimer pathology biomarkers in elderly people with multiple sclerosis

Objectives: Neurofilament light chain (NfL) conventionally reflects disability worsening in multiple sclerosis (MS), but does not necessarily imply MS-specific mechanisms and could be affected by biological or pathological aging, including Alzheimer disease (AD) pathology. We aim to evaluate clinical correlates of plasma NfL (pNfL) in elderly patients with MS, and its associations with AD plasma biomarkers. Methods: We recruited consecutive people with MS >65 years, and collected expanded disability status scale (EDSS), current disease modifying treatment (DMT) and years of exposure to DMTs. Cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMTR). Plasma biomarkers (Aβ40, Aβ42, p-Tau181, and pNfL) were measured using LUMIPULSE assay kits on the CLEIA analyser LUMIPULSE G600II. Results: We included 83 elderly adults (age 68.8 ± 3.1 years; females 65.8 %) with MS (EDSS 5.5 (2.0–8.0)). On linear regression models adjusted for age, sex, BMI, smoking status, and cardiovascular risk factors, there were no associations between pNfL and EDSS, type and duration of DMT exposure, SDMT, CVLT, and BVMRT. Higher pNfL was associated with lower plasma Aβ40 (Coeff = −0.40; 95 %CI = -0.66, −0.14; p = 0.003), plasma Aβ42 (Coeff = −4.46; 95 %CI = -7.92, −1.00; p = 0.01), and Aβ42/Aβ40 ratio (Coeff = −2612.06; 95 %CI = -4114.76, −1109.36; p = 0.001). Also, lower Aβ42/Aβ40 ratio was associated with impaired CVLT (Coeff = −0.021; 95 %CI = -0.036, −0.006; p = 0.007). Interpretation: pNfL in elderly people with MS is associated with biomarkers of amyloid accumulation, which in turn are associated with cognitive impairments, suggesting overlapping pathologies between MS and AD.