Aggregation of tau proteins in filamentous inclusions is a common feature of several neurodegenerative disorders. The laminar and regional distributions of NFT or other inclusions differ among conditions associated with dementia. The electrophoretic pro-files of pathological tau proteins permit classification of these diseases on a basis of their biochemical signatures. These profiles may be explained by selective aggregation of specific sets of tau isoforms, differential vulnerability of neuronal subpopu lations, and possibly variable sets of enzymes (kinases and/or phosphatases) that affect the phosphorylation state of the tau isoforms [1,21,25].

Mapping of the spatiotemporal distribution of tau pathology in different brain areas is important in understanding how the disease spreads in the brain. While tau gene mutations simultaneously affect different brain areas, many sporadic tauopathies affect first a specific vulnerable area, e.g., the entorhinal cortex and hippocampal area in AD, the brainstem in PSP and CBD. The extension of tauopathy in AD correlates with the evolution of cognitive deficits, from memory disorders to language impairment and then to apraxia and agnosia. It is interesting that the tau pathologies in PSP and CBD are quite different from those seen in AD, since they emerge from subcortical nuclei toward the neocortex, especially toward frontal motor cortex [25]. Overall, the results discussed here, indicate that the key event in the tauopathies is disorganization of the cytoskeleton that leads to nerve cell degeneration, whether the primary cause is a tau gene mutation and/or polymorphism or some other unidentified factors.