Age-related neurofilament phosphorylation in normal human brains

An age-related phosphorylation of the 200kD neurofilament protein (NF200) has been observed in the axons of cerebellar basket cells of normal human fixed brain tissue from individuals older than 60 years, but not in younger individuals. The probe for this study was the monoclonal antibody SMI-34 which detects a phosphorylated epitope on NF200 which appears to be different from the more frequent NF200 phosphorylated epitope found by another monoclonal antibody, SMI-31. The SMI-31 epitope was detected in our specimens at all ages examined. In sections of brainstems from normal individuals older than 52 years, from Alzheimer's disease individuals older than 65 years and from older Down's syndrome individuals (greater than 56 years) certain axons in the medial longitudinal fasciculus and in the mesencephalic trigeminal tract react positively with SMI-34, the antibody which detects the "age-related" phosphorylation epitope. All our Alzheimer's disease specimens and all our Down's syndrome specimens, even the younger ones, show staining of these fibers with SMI-31. The biochemistry of the "age-related" phosphorylation of NF200 remains to be explained.