Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study

Aims: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN). Materials and Methods: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini-Hochberg procedure. Results: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), p(B-H) = 0.044) and PDGFR alpha (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), p(B-H) = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all p(B-H) for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all p(B-H)>0.05). Conclusions: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.