Abnormal tau proteins and neuronal degeneration in Alzheimer's disease

Summary

Dementia in Alzheimer's disease is associated closely with the accumulation of hyperpkosphorylated, C-terminally truncated tau protein. It is accumulated, in part, into paired helical filaments (PHF) which form the neurofibrillary tangles characteristic of the disease. The accumulation of this abnormal tau protein creates a tau 'sink’ which, by depleting normal tau, results in the depolymerization of microtubules, the failure of microtubule-dependent intraneuronal transport systems, and ultimately, in the degeneration of neurons. This degenerative process may be modelled by the effect of heat shock on nerve growth factor (NGF)-differentiated PC 12 cells in vitro. The model, which suggests that neuronal degeneration in Alzheimer's disease may be associated with interactions between abnormal tau protein, microtubules and mitochondria, allows these three reactants to be manipulated experimentally. It may prove useful in the development of pharmaceutical agents that inhibit the formation of abnormal tau proteins, encourage their destruction, or counteract their effect.