The mutation causing myotonic dystrophy (DM) is an unstable CTG trinucleotide repeat in a gene encoding for a protein with putative serine-threonine kinase activity. Several studies have reported the appearance of abnormally frequent neurofibrillary tangles (NFTs) in the cortex of patients with DM. Using immunologic probes against normal and pathologic hyperphosphorylated tau proteins, the basic components of NFTs, we performed a biochemical and immunohistochemical study of the brains of two DM cases. We compared the tau profiles with those found in Alzheimer's disease (AD) using mono- and two-dimensional immunoblotting. Patients were aged 53 and 61 years at death. In both cases, we observed few perikaryal and axonal inclusions in the hippocampus as well as the entorhinal and inferior temporal cortices. As in AD brain homogenates, pathologic tau proteins, named tau 55, 64, and 69, were exclusively immunodetected in the DM cases in the hippocampus, the entorhinal cortex, and in most of the temporal areas. Amounts of pathologic tau proteins were higher in the more severely affected case, but lower than in AD brain homogenates. Pathologic tau proteins were less acidic in DM than in AD. We found a very low amount of the tau 69 isoform in DM extracts, and in most of the cortical areas, tau 55 was overexpressed compared with AD homogenates. A link between the increase of kinase activity and the presence of pathologic tau proteins is discussed.

NEUROLOGY 1996;47: 711-717