Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

PURPOSE: Reactivation of neurodevelopmental processes may contribute to neurodegeneration. For example, the proteins cyclin dependent kinase 5 (cdk5) and glycogen synthase kinase 3 beta (GSK3beta), which are essential to normal cortical development, can hyperphosphorylate tau and might contribute to the pathogenesis of Alzheimer's disease. Focal cortical dysplasia (FCD) is an important neurodevelopmental cause of refractory human epilepsy within which dysplastic neurons exhibit increased immunoreactivity for cdk5 and GSK3beta as well as neurofilamentous accumulations. We therefore hypothesized that the developmentally abnormal cortex of FCD might be more susceptible to tau-mediated neurodegeneration than adjacent histologically normal cortex. MATERIALS AND METHODS: We examined a series of 15 cases of FCD, spanning a wide age range, for beta-amyloid, pathologically phosphorylated tau and neurofibrillary tangles using silver staining, immunohistochemistry for tau, AT8, RD3, RD4 and two-dimensional cell counting. RESULTS: Beta-amyloid plaques, aberrantly phosphorylated tau and neurofibrillary tangles are only found in older patients. The hyperphosphorylated tau tangles are confined to dysplastic neurons. Immunoreactivity for 3- and 4-repeat tau was again only detected within regions of FCD in older patients. With increasing age, the dysplastic cortex became hypocellular and a higher proportion of dysplastic neurons exhibited pathological tau phosphorylation. CONCLUSIONS: In older patients, FCD appears more susceptible to formation of pathologically phosphorylated tau neurofibrillary tangles than adjacent histologically normal cortex. Our results suggest a novel convergence of pathological neurodevelopment with pathological age-related neurodegeneration.

Original publication

DOI

10.1111/j.1528-1167.2007.01107.x

Type

Journal article

Journal

Epilepsia

Publication Date

08/2007

Volume

48

Pages

1447 - 1454

Keywords

Adolescent, Adult, Age Factors, Aged, 80 and over, Amyloid beta-Peptides, Cell Count, Cerebral Cortex, Child, Child, Preschool, Coloring Agents, Epilepsies, Partial, Female, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, Immunohistochemistry, Infant, Male, Middle Aged, Nerve Degeneration, Neurofibrillary Tangles, Neurons, Phosphorylation, Tauopathies, tau Proteins