title: Review. David Oppenheimer Memorial Lecture 1995: Some neuropathological aspects of Alzheimer's disease and its relevance to other disciplines.
abstract: Recent studies of diffuse A beta plaques point to the neurons as a source of A beta 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 A beta 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 beta-APP. There is also a myocyte tissue culture model in which both soluble and fibrillized A beta are found. The relationship between A beta and neurofibrillary pathology is not clear and the current cascade hypothesis proposing that A beta pathology drives the formulation of neurofibrillary tangles is being questioned. There is growing evidence that it is not the A beta hypothesis, but the co-existing A beta neurofibrillary tangle pathology hypothesis which will be the basis for AD neuropathology.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314-6399, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Wisniewski
authors.forename: J
authors.initials: J
authors.lastname: Wegiel
authors.forename: L
authors.initials: L
authors.lastname: Kotula
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice
chemical_list: D016564:Amyloid beta-Protein Precursor