Identification of Gal(β1-3)GalNAc bearing glycoproteins in cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients

Glycoproteins in cerebrospinal fluid of 55 patients with amyotrophic lateral sclerosis (ALS), six disease controls (multifocal motor neuropathy, sensorimotor neuropathy, Guillain-Barre syndrome, spinal muscular atrophy type II, motor neuropathy with monoclonal gammopathy) and 20 healthy controls were separated by PAGE electrophoresis and then detected immunochemically with peanut agglutinin (PNA). In 36 amyotrophic lateral sclerosis patients the 262 kDa glycoprotein was significantly increased (over the normal mean +/- SD x 2), which was associated with a decrease in the 114 kDa fraction. In the remaining patients, both fractions were either equal in concentration or the 114 kDa glycoprotein predominated. In normal cerebrospinal fluid, the 114 kDa glycoprotein predominated over the other glycoproteins. The total amount of separated glycoproteins was increased in 15 amyotrophic lateral sclerosis patients. In 12 of them it was followed by an increase in the percentage of the 262 kDa glycoprotein. There was no correlation between the content of the peanut agglutinin-labelled glycoproteins and the patients' age, duration and severity of the disease. There was a correlation between the 262 kDa glycoprotein being increased in cerebrospinal fluid and the electrophysiological pattern of denervation seen in electromyographic study. The glycoproteins change, similar to that occurring in amyotrophic lateral sclerosis patients, was also observed in one case of multifocal motor neuropathy (MMN). We suggest that in amyotrophic lateral sclerosis and multifocal motor neuropathy, the peanut agglutinin-labelled glycoproteins are released in excess from the nervous tissues into the cerebrospinal fluid as a result of neuronal degeneration. The question to be answered is, whether the released glycoproteins are becoming targets for auto-antibodies.