Human endogenous retrovirus K (HERV-K) env in neuronal extracellular vesicles: a new biomarker of motor neuron disease

Objective: Human endogenous retroviruses (HERVs) have been gradually confirmed to be involved in the onset and progression of motor neuron disease(MND). However, noninvasive detection of HERVs in the central nervous system is lacking. The aim of this study is to verify the relationship between the level of HERV-K env in neuronal extracellular vesicles in plasma and the onset and severity of MND. Methods: We extracted neuronal extracellular vesicles from plasma of 39 MND patients and 30 age- and sex-matched controls, and detected HERV-K env in extracellular vesicles by an enzyme-linked immunosorbent assay (ELISA). Results: Levels of HERV-K env in neuronal extracellular vesicles positively associated with range of lower motor neurons (LMNs) involved (1.66 ± 0.37 vs. 1.35 ± 0.34, p = 0.041), ALS phenotype (1.52 ± 0.31 vs. 1.24 ± 0.37, p = 0.013) and course of disease (1.83 ± 0.35 vs. 1.42 ± 0.22, p = 0.003), and increased in advanced-phase MND (definite and probable according to revised EI Escorial criteria) compared with early-phase MND (possible and lab-supported probable), albeit without very profound significance (1.52 ± 0.34 vs. 1.29 ± 0.36, p = 0.048). Conclusions: In conclusion, levels of HERV-K env in neuronal extracellular vesicles extracted from plasma can be used as a noninvasive biomarker of severity of MND.