FAMILIAL MULTIPLE SYSTEM TAUOPATHY WITH PRESENILE-DEMENTIA - A DISEASE WITH ABUNDANT NEURONAL AND GLIAL TAU-FILAMENTS

Neurofibrillary lesions made of hyperphosphorylated microtubule-associ ated protein tau constitute not only one of the defining neuropatholog ical features of Alzheimer disease but also are present in a number of other neurodegenerative diseases with dementia. Here we describe a no vel autosomal dominant disease named familial ''multiple system tauopa thy with presenile dementia,'' which is characterized by abundant fibr illary deposits of tau protein in both neurons and glial cells. There are no detectable deposits of P-amyloid. The tau deposits are in the f orm of twisted filaments that differ in diameter and periodicity from the paired helical filaments of Alzheimer disease. They are stained by both phosphorylation-independent and -dependent anti-tau antibodies. Moreover, tau immunoreactivity coexists with heparan sulfate in affect ed nerve and glial cells. Tau protein extracted from filaments of fami lial multiple system tauopathy with presenile dementia shows a minor 7 2-kDa band and two major bands of 64 and 68 kDa that contain mainly hy perphosphorylated four-repeat tau isoforms of 383 and 412 amino acids.