A disease propagation and progression model, composed of six stages of increasing pathological severity determined by the location of the tangle-bearing neurons and the amplitude of the pathophysiological changes.Limbic stages III-IV designate an incipient Alzheimer's disease, since due to the lack of neocortical destruction, stages III and IV do not meet the currently used criteria for neuropathologic diagnosis of AD. Stage III is characterised by the destruction of the external principal stratum of the entorhinal laminae presenting considerable amounts of NFT and neuropil threads.