SPECIFIC TAU VARIANTS IN THE BRAINS OF PATIENTS WITH MYOTONIC-DYSTROPHY

The mutation causing myotonic dystrophy (DM) is an unstable CTG trinuc leotide repeat in a gene encoding for a protein with putative serine-t hreonine kinase activity, Several studies have reported the appearance of abnormally frequent neurofibrillary tangles (NFTs) in the cortex o f patients with DM. Using immunologic probes against normal and pathol ogic hyperphosphorylated tau proteins, the basic components of NFTs, w e performed a biochemical and immunohistochemical study of the brains of two DM cases. We compared the tau profiles with those found in Alzh eimer's disease (AD) using mono- and two-dimensional immunoblotting. P atients were aged 53 and 61 years at death. In both cases, we observed few perikaryal and axonal inclusions in the hippocampus as well as th e entorhinal and inferior temporal cortices. As in AD brain homogenate s, pathologic tau proteins, named tau 55, 64, and 69, were exclusively immunodetected in the DM cases in the hippocampus, the entorhinal cor tex, and in most-of the temporal areas. Amounts of pathologic tau prot eins 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 ext racts, and in most of the cortical areas, tau 55 was overexpressed com pared with AD homogenates. A link between the increase of kinase activ ity and the presence of pathologic tau proteins is discussed.