The expression of neurofilament (NF)
proteins was examined in the surgical specimen from a 42-year-old woman with
Lhermitte-Duclos disease. Hypertrophic granule cell neurons of the dysplastic tissues were reactive with
monoclonal antibodies, including
antibodies to each of the three human NF subunits. Furthermore,
antibodies to dephosphorylation-dependent
epitopes on NF
proteins stained the cell bodies of hypertrophic granule cells, whereas
antibodies to phosphorylation-dependent
epitopes stained the enlarged and myelinated axons of the hypertrophic granule cells. Enzymatic dephosphorylation of this tissue abolished axonal staining with phosphorylation-dependent
antibodies and uncovered determinants recognized by
antibodies to the dephosphorylated state of NF
proteins. The NF
protein immunoreactivity of hypertrophic granule cells was indistinguishable from that of large, NF-rich neurons in control human cerebellum, suggesting that a normal pattern of expression and phosphorylation of NF
proteins occurs in hypertrophic granule cells in
Lhermitte-Duclos disease. An increased expression of NF
proteins by cerebellar granule cells may account for many of the observed alterations of
Lhermitte-Duclos disease, including the
hypertrophy of the granule cells and enlargement of their axons, leading to the myelination of parallel fibers within the molecular layer of the cerebellum. Attention should now be directed at the underlying mechanisms which lead to the coordinated up-regulation of the three NF genes and whether or not additional gene products or cell types are altered in
Lhermitte-Duclos disease.