SOME NEUROPATHOLOGICAL ASPECTS OF ALZHEIMERS-DISEASE AND ITS RELEVANCE TO OTHER DISCIPLINES

Recent studies of diffuse A beta plaques point to the neurons as a sou rce of A beta in diffuse plaques. The neuritic (primitive and classica l) plaques appear to be the product of microglia and the myocytes are the source of amyloid deposits in the meningeal and cortical vessels. Dyshoric angiopathy is associated with deposits of amyloid by perivasc ular cells, Fibrillization of the neuron-derived diffuse, thioflavine- negative or benign plaques is poor or undetectable by current morpholo gical methods including ultrastructural immunocytochemistry. It appear s that fibrillization depends on the length of the A beta peptides and on the presence of amyloid-associated proteins. Four genes are now ti ghtly linked with Alzheimer's disease (AD) and they are located on chr omosomes 21, 19, 14 and 1. Therefore, AD should be considered a polyae tiological disease or syndrome. There are currently five transgenic mo use models overexpressing beta-APP. There is also a myocyte tissue cul ture model in which both soluble and fibrillized A beta are found, The relationship between A beta and neurofibrillary pathology is not clea r and the current cascade hypothesis proposing that A beta pathology d rives the formulation of neurofibrillary tangles is being questioned. There is growing evidence that it is not the A beta hypothesis, but th e co-existing A beta neurofibrillary tangle pathology hypothesis which will be the basis for AD neuropathology.