Four different approaches to Alzheimer disease changes have been successively applied, and allowed a permanent feed forward-feed back enrichment of knowledge: morphologists described neurofibrillary tangles, senile plaques, amyloid angiopathy; with the help of immunohistochemical and biochemical techniques, they recognised A beta- and tau-associated pathologies; this, in turn, allowed more precise analysis of the lesions, and permitted recognising new ones such as neuropil threads; molecular genetics and molecular biology provided new insights, allowing the discovery of additional pathologic proteins, the relevance of which to physiology and pathology of the nervous system has now to be settled down. The increasingly intricate complex of lesions of Alzheimer syndrome is reviewed. A more comprehensive understanding is urgently needed for initiating efficient therapeutic researches. It will require together continuing a multidisciplinary approach, and a renewal of research in neuropathology.