Tau pathology and neurodegeneration: an obvious but misunderstood link.

Most dementing disorders result from a degenerating process named tauopathy. Alzheimer disease is the most frequent one, but only one among the large spectrum of tau-related diseases. Cognitive impairment is related, first of all, to the neocortical location of this degenerating process. However, the nature and the mechanisms leading to tauopathy can be very different. This is demonstrated by familial mutations on the tau gene as well as by the different morphological and biochemical patterns of tau lesions. Therefore there is no doubt that tau is an etiological agent. But the persistent and unsolved question is the basic mechanism leading to neurodegeneration: is it due to the toxic effect of aggregated tau, or a loss of tau function, or both? Some answers may come from a more focused interest towards sporadic tauopathies. Most of them are characterized by a degenerating process starting in a specific and vulnerable brain area and consuming the connected neuronal network, like a chain reaction. In other words, sporadic tauopathies are mostly a destabilization of specific neuronal networks that should be modeled for an efficient therapeutic approach.