Abstract
Tauopathies are neurodegenerative diseases characterized behaviorally by dementia and neuropathologically by neurofibrillary tangles and neuronal loss. Tau gene mutations have been found in frontotemporal dementia with parkinsonism linked to chromosome 17, suggesting that mutation of tau induces tauopathy. Studies on in vitro tau aggregation show that tau forms two different intermediate aggregates—called tau oligomers and granular tau oligomers—before forming fibrils. Moreover, studies using a mouse model that expresses human tau demonstrated that the process of neurofibrillary tangle formation, rather than tangles themselves, may cause synapse loss and neuron loss. Further analyses suggest that hyperphosphorylated tau or oligomeric tau is involved in synaptic loss, whereas granular tau oligomers are responsible for neuronal loss. Thus, different forms of tau aggregates are involved in the different pathological changes that occur in tauopathies.