, Volume 87, Issue 5, pp 493-503

Neuronal cytoskeletal abnormalities in human cerebral cortical dysplasia

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Abstract

The cytoskeletal abnormalities of cortical neurons in human cerebral cortical dysplasia were compared by immunohistochemical methods to the neurofibrillary tangles of Alzheimer's disease (AD). Surgical specimens from cortical resections performed for the treatment of intractable childhood seizures as well as autopsied samples from AD patients were analyzed with different antibodies directed against high- or medium-molecular mass neurofilament epitopes, phosphorylated or non-phosphorylated forms of neurofilaments, ubiquitin, the microtubule-associated protein tau, and paired helical filaments (PHF), a defining feature of AD tangles. A strong abnormal increase in immunoreactivity to the high and medium molecular mass neurofilament epitopes was seen in hypertrophic neurons of cortical dysplasia. These neurofilamentous accumulations of cortical dysplasia as well as AD tangles also displayed immunoreactivity with antibodies also displayed immunoreactivity with antibodies against phosphorylated and non-phosphorylated neurofilament epitopes, tau and ubiquitin. Only the AD tangles, however, were immunoreactive to the antiserum to PHF. These results replicate and extend our previous findings that the neurofibrillary accumulations in cerebral cortical dysplasia share some common antigens with the neurofibrillary tangles of AD but do not demonstrate immunoreactivity to PHF antiserum. The results also suggest that the cytoskeletal abnormalities observed in neurons of cortical dysplasia may result in part from alterations in the level of expression, in phosphorylation state or in transport of cytoskeletal components.

Supported by NIH Training Grant HD 07032 (T.D.), NIH NS28383 (M.J.D., R.S.F., H.V.V.), NIH NS24596 (R.S.F.) and NIH NS26312 (H.V.V.). Ongoing work of the UCLA Pediatric Epilepsy Group is supported by the Milken Family Medical Foundations