However, deposition of amyloidplaques does not always correlatewell with neuron loss. Thisobservation supports the tauhypothesis, the idea that tau proteinabnormalities initiate the diseasecascade.• Formation of neuritic plaques wouldinstigate further pathological events,including the formation of pairedhelical filaments (PHFs).• PHFs contribute to Neurofibrillarytangles (NFT) protein aggregates thatalong with senile plaques, are theaberrant structures found in thebrains of patients with AD.• NFTs are intraneuronal lesionscomposed primarily (95%) of PHFs.• Tau (τ) as the major PHFscomponent of the was