| Abstract: | Recent studies of diffuse Aβ plaques point to the neurons as a source of Aβ in diffuse plaques. The neuritic (primitive and classical) 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 perivascular cells. Fibrillization of the neuron-derived diffuse, thioflavine-negative or benign plaques is poor or undetectable by current morphological methods including ultrastructural immunocytochemistry. It appears that fibrillization depends on the length of the Aβ peptides and on the presence of amyloid-associated proteins. Four genes are now tightly linked with Alzheimer's disease (AD) and they are located on chromosomes 21, 19, 14 and 1. Therefore, AD should be considered a polyaetiological disease or syndrome. There are currently five transgenic mouse models overexpressing β-APP. There is also a myocyte tissue culture model in which both soluble and fibrillized Aβ are found. The relationship between Aβ and neurofibrillary pathology is not clear and the current cascade hypothesis proposing that Aβ pathology drives the formulation of neurofibrillary tangles is being questioned. There is growing evidence that it is not the Aβ hypothesis, but the co-existing Aβ neurofibrillary tangle pathology hypothesis which will be the basis for AD neuropathology. |
