Comparative study of CSF neurofilaments in HTLV-1-associated myelopathy/tropical spastic paraparesis and other neurological disorders

Abstract

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive CNS disease leading to corticospinal tract degeneration. Various degenerative diseases have increased neurofilament subunit concentration in cerebrospinal fluid (CSF), frequently showing hyperphosphorylation in neurofilaments. The aim of this study was to determine if there were elevated concentrations of neurofilament light subunit (NFL) and phosphorylated forms of neurofilament heavy subunit (PNFH) in HAM/TSP CSF. NF concentrations were compared with those of controls and patients with neurodegenerative diseases associated with other retroviruses (HIV-associated dementia, HAD) and a form of prion disease (familiar Creutzfeldt-Jakob, FCJD). Western blotting of CSF with antibodies against NFL showed two immunoreactive bands of 66 and 59 kDa, the latter probably corresponding to a partially degraded NFL form. The concentration of the 59-kDa form was not different in HAM/TSP compared with controls, but it was significantly increased in HAD and FCJD groups. ELISA assay for PNFH did not show differences among HAM/TSP, HAD, and control groups, while PNFH concentration was significantly elevated in FCJD. Our results show that CSF NFL and PNFH are not molecular markers of axonal damage for HAM/TSP probably due to the slow progression of this disease. NFL phosphorylation studies required previous immunoprecipitation from CSF for mass spectrometric analysis. This preliminary analysis indicated phosphorylation at S472 and at some other residues.