Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis.
We used a library of monoclonal antibodies (Mab) that distinguish phosphorylated (P+) and non-phosphorylated (P-) neurofilament (NF) epitopes to examine phosphorylation of NF in lower motor neurons of patients with amyotrophic lateral sclerosis (ALS), of neurologically normal controls of different ages, and of patients with central chromatolysis due to injuries to motor root axons. Monoclonal antibodies directed to P+ NF immunostained five to ten times more neuronal perikarya in ALS than in age-matched controls. Spheroids, which are NF containing axonal enlargements, found in significantly greater number in proximal axons in ALS, were also intensely immunostained with Mab to P+ NF. Moreover, anterior root axons in five of eleven cases of ALS reacted only with the Mab to P+ NF, while both P- and P+ NF were present in motor roots from controls. In control groups, the number of neuronal perikarya and spheroids that immunoreacted with the Mab to P+ NF increased moderately with age. Chromatolytic lower motor neurons were recognized by Mab to P+ NF. Our results show that the process of phosphorylation is altered in ALS. We propose that phosphorylation of NF in ALS occurs prematurely and that it is more likely to be associated with an impairment of NF transport than to be part of a chromatolytic reaction of lower motor neurons.
Manetto
V
V
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Sternberger
N H
NH
Perry
G
G
Sternberger
L A
LA
Gambetti
P
P
D000328:Adult; D000368:Aged; D000375:Aging; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D007382:Intermediate Filaments / Q000378:metabolism* / Q000648:ultrastructure; D008875:Middle Aged; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D012016:Reference Values; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D000939:Epitopes