EPITOPE EXPRESSION AND HYPERPHOSPHORYLATION OF TAU-PROTEIN IN CORTICOBASAL DEGENERATION - DIFFERENTIATION FROM PROGRESSIVE SUPRANUCLEAR PALSY

Corticobasal degeneration (CBD) is a rare, progressive neurological di sorder characterized by widespread neuronal and glial accumulation of abnormal tau protein. Using immunohistochemistry we analyzed tau epito pe expression and phosphorylation state in CBD and compared them to cy toskeletal changes in Alzheimer's disease (AD) and progressive supranu clear palsy (PSP). Epitopes spanning the entire length of the tau prot ein were present in CBD inclusions. An antibody against the alternativ ely spliced exon 3 did not recognize cytoskeletal lesions in CBD, but did in AD and PSP. Tau epitopes from each region of the molecule were present in cytoskeletal inclusions in CBD, including gray matter astro cytic plaques, gray and white matter threads, and oligodendroglial inc lusions. As in AD, tau from CBD was highly phosphorylated. Antibodies that recognized phosphorylated tau epitopes reacted with material from CBD in a highly phosphatase-dependent manner. Again, all types of inc lusions contained phosphorylated epitopes. We conclude that abnormal t au protein in CBD comprises the entire tau molecule and is highly phos phorylated, but is distinguished from AD and PSP by the paucity of epi topes contained in the alternatively spliced exon 3.