Biochemical and molecular characterization of neurofibrillary degenerationin frontotemporal dementias

Neurofibrillary degeneration (NFD) is a degenerating process characterized by the intraneuronal aggregation of abnormal tau proteins. These proteins h ave a biochemical signature which is disease-specific. They also have a neo cortical distribution which is typical of the disease. Pathological tau pro teins have been analyzed qualitatively and quantitatively in all diseases t hat may present the clinical symptoms of frontotemporal dementias. In Alzhe imer's disease, a disease with sometimes a frontal predominance, paired hel ical filaments (PHF) of neurofibrillary tangles are made of hyperphosphoryl ated tau, named PHF-tau. Their electrophoretic profile consists of four mai n bands (tau 55, 64, 69, 74 kD), resulting from the presence of the six tau isoforms. In Pick's disease the phosphorylated tau from Pick bodies are ma de of two major components (tau 55, 64 kD) and a minor 69 kD resulting from the lack of tau isoforms with the translated exon 10 (E10-). Corticobasal degeneration (CBD) also has a different pattern of tau variants, with tau 6 4, 69 components and a minor tau 74. Pathological tau proteins that aggrega te in CBD (and progressive supranuclear palsy) are exclusively made of E10 tau isoforms. In frontotemporal dementias non-Alzheimer, non-Pick (Lund an d Manchester criteria), we did not observe the presence of pathological tau proteins in 2 cases, but a third one presented a particular pattern of tau , with soluble pathological tau in frontotemporal areas. These data show th at this group could be heterogeneous. In conclusion, the biochemical signat ure of tau distinguishes four classes of frontotemporal dementia. The chara cteristic tau phenotypes observed are linked to the specific neuronal netwo rks that are affected in each disease.