Different configurational states of beta-amyloid and their distributions relative to plaques and tangles in Alzheimer disease.

Antibodies have been raised against synthetic peptides corresponding to different parts of the beta-amyloid sequence. These antibodies stain different kinds of amyloid distributions in the hippocampal formation in Alzheimer disease, suggesting the existence of different states of aggregation and/or folding of beta-amyloid molecules. An antibody directed against the middle region of beta-amyloid stained mostly amyloid plaques without cores, whereas an antibody directed against the carboxyl-terminal region of beta-amyloid stained only amyloid plaques with cores. An antiserum directed against the amino terminus of beta-amyloid stained numerous tangle-bearing cells and bodies, as well as the neuritic component of plaques and neuropil threads. These antibodies, in conjunction with anti-tau antibodies, were used to demonstrate a close spatial relationship between amyloid deposits and neurofibrillary tangles.